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1
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Do TT, Bui LNV, Nguyen L, Le LN, Tran DTP. Clinical and Pathological Features of Oral Cancer in a High-Risk Community in Vietnam. J Maxillofac Oral Surg 2025; 24:241-245. [PMID: 39902410 PMCID: PMC11787134 DOI: 10.1007/s12663-023-01997-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2023] [Accepted: 08/08/2023] [Indexed: 02/05/2025] Open
Abstract
Background Oral cancer (OC) is the sixth most common cancer worldwide. There have been few studies on OC in high-risk populations. This study aimed to describe the clinical features, staging, grading, and risk factors in OC patients. Methods This cross-sectional study was conducted on 109 OC patients diagnosed and treated from April 2018 to May 2020. The patients were identified using eData. Results The average age of the patients was 60.32 ± 12.4 years, and the male-to-female ratio was 2.9:1. The most common site for OC was the tongue (37.6%), and oral squamous cell carcinoma was the most common histopathology (84.4%). The most common clinical forms were verruca (37.6%) and erosive ulcers (33.9%). Most patients were in stage III or IV (71.6%). Average time of detection was 7.32 ± 17.12 months. Conclusions OC occurs most often in elderly people, males, and is diagnosed late. The main risk factors are smoking and consuming alcohol.
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Affiliation(s)
- Thao Thi Do
- Faculty Odonto-Stomatology, Can Tho University of Medicine and Pharmacy, Can Tho, Vietnam
| | | | - Lam Nguyen
- Faculty Odonto-Stomatology, Can Tho University of Medicine and Pharmacy, Can Tho, Vietnam
| | - Lam Nguyen Le
- Faculty Odonto-Stomatology, Can Tho University of Medicine and Pharmacy, Can Tho, Vietnam
| | - Dan Thi Phuong Tran
- Faculty Odonto-Stomatology, Can Tho University of Medicine and Pharmacy, Can Tho, Vietnam
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2
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Mei B, Zeng Z, Xia Q, Liu M, Zhang Y. The role of the circ_DOCK1-miR-1297-HOXA9 regulatory network in the development of oral squamous cell carcinoma. Pathol Res Pract 2025; 266:155752. [PMID: 39721095 DOI: 10.1016/j.prp.2024.155752] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2024] [Revised: 10/24/2024] [Accepted: 12/01/2024] [Indexed: 12/28/2024]
Abstract
OBJECTIVE Oral squamous cell carcinoma (OSCC) is a public health concern. The current study aimed to explore the role of circRNA Dedicator of Cytokinesis 1 (circ_DOCK1) and associated action mode in OSCC. METHODS The expression of circ_DOCK1 and microRNA-1297 (miR-1297) was measured by quantitative real-time polymerase chain reaction (qRT-PCR). EdU assay, colony formation assay, transwell assay and glycolysis stress test were applied for functional analyses. The expression level of Homeobox A9 (HOXA9) was detected by western blot. The interaction between miR-1297 and circ_DOCK1 or HOXA9 was verified by dual-luciferase reporter assay. Xenograft model was established to determine the role of circ_DOCK1 in vivo. RESULTS Circ_DOCK1 was highly expressed in OSCC tumor tissues and cell lines. Circ_DOCK1 knockdown suppressed colony formation, migration, invasion and glycolysis of OSCC cells. MiR-1297 was targeted by circ_DOCK1, and its inhibition reversed the anticancer effects of circ_DOCK1 knockdown. HOXA9 was a target of miR-1297, and its overexpression recovered miR-1297 reintroduction-evoked inhibition of colony formation, migration, invasion and glycolysis in OSCC cells. Furthermore, circ_DOCK1 knockdown repressed tumor growth in vivo. CONCLUSION Circ_DOCK1 exerted its carcinogenic role in OSCC partially via the circ_DOCK1-miR-1297-HOXA9 regulatory network, which will broaden our insights to understand the pathogenesis of OSCC and provide promising biomarkers for the diagnosis and treatment of OSCC.
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Affiliation(s)
- Bingxin Mei
- Department of Stomatology, The First Affiliated Hospital Of Gannan Medical University, Ganzhou, China
| | - Zhimei Zeng
- Department of Stomatology, The First Affiliated Hospital Of Gannan Medical University, Ganzhou, China
| | - Qinmin Xia
- Department of Stomatology, The First Affiliated Hospital Of Gannan Medical University, Ganzhou, China
| | - Ming Liu
- Department of Stomatology, The First Affiliated Hospital Of Gannan Medical University, Ganzhou, China
| | - Ying Zhang
- Department of Stomatology, The First Affiliated Hospital Of Gannan Medical University, Ganzhou, China.
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3
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Li X, Xue D, Wei Q, Tan X. Serum KL-6 levels reflect the severity of interstitial lung disease caused by immune checkpoint inhibitors. Immunobiology 2025; 230:152866. [PMID: 39798404 DOI: 10.1016/j.imbio.2024.152866] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2024] [Revised: 12/05/2024] [Accepted: 12/30/2024] [Indexed: 01/15/2025]
Abstract
Tumor immunotherapy, particularly immune checkpoint inhibitors (ICIs), has emerged as a powerful strategy in treating malignant tumors, exhibiting efficacy in both first-line and second-line treatments for advanced non-small cell lung cancer (NSCLC). Despite their success, ICIs can lead to adverse reactions, including interstitial lung disease (ILD), with an incidence ranging from 2.7 % to 20.0 %. The lack of clear correlations with dosage, duration, or drug efficacy, coupled with nonspecific clinical manifestations, poses challenges in timely diagnosis and effective management. This study examined the association between ICIs-related ILD and serum levels of KL-6 and inflammatory markers in NSCLC patients. A total of 382 NSCLC patients with squamous cell carcinoma (SQC, n = 81), adenocarcinoma (ACA, n = 132), and large cell carcinoma (LCC, n = 169) were included, of whom 191 developed ILD following ICIs treatment. Serum KL-6, TNF-α, IL-8, and IL-6 were quantified using ELISA. Results showed significantly elevated serum KL-6 levels in ILD patients (759.35 ± 214.14 U/mL) compared to those without ILD (270.81 ± 124.98 U/mL). Cancer subtype analysis revealed increased KL-6 levels across SQC, ACA, and LCC ILD patients (SQC: 645.89 ± 255.07, ACA: 797.39 ± 192.30, LCC: 783.57 ± 191.21; p < 0.001). ROC analysis identified diagnostic thresholds for KL-6: 277.4 U/mL for SQC (sensitivity 0.9756, specificity 0.8250), 346.9 U/mL for ACA (sensitivity 0.9583, specificity 0.8333), and 281.3 U/mL for LCC (sensitivity 0.9873, specificity 0.6111). Correlation analysis showed a significant relationship between KL-6 and TNF-α (r = 0.4626, p = 0.0023), IL-8 (r = 0.5584, p = 0.0001), and IL-6 (r = 0.5336, p = 0.0003) in SQC ILD patients. These findings suggest that elevated KL-6 levels and inflammatory markers are indicative of ILD in ICIs-treated NSCLC patients, with potential diagnostic implications across cancer subtypes.
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Affiliation(s)
- Xiaoping Li
- Department of Respiratory and Critical Care Medicine, Fujian Medical University Union Hospital, China.
| | - Dan Xue
- Department of Respiratory and Critical Care Medicine, Fujian Medical University Union Hospital, China
| | - Qiongying Wei
- Department of Respiratory and Critical Care Medicine, Fujian Medical University Union Hospital, China
| | - Xuexue Tan
- Department of Respiratory and Critical Care Medicine, Fujian Medical University Union Hospital, China
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Li BJ, Ren FH, Zhang C, Zhang XW, Jiao XH. LncRNA AFAP1-AS1 Promotes Oral Squamous Cell Carcinoma Development by Ubiquitin-Mediated Proteolysis. Int Dent J 2024; 74:1277-1286. [PMID: 38914506 PMCID: PMC11551608 DOI: 10.1016/j.identj.2024.04.024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2023] [Revised: 04/18/2024] [Accepted: 04/24/2024] [Indexed: 06/26/2024] Open
Abstract
BACKGROUND AND PURPOSE Long noncoding RNA (lncRNA) dysregulation has been reported to play a pivotal role in the development of cancers. In this study, we aimed to screen the key lncRNA in oral squamous cell carcinoma (OSCC) via bioinformatics analysis and further validate the function of lncRNA in vitro and in vivo. METHODS Bioinformatics analysis was conducted to identify differentially expressed lncRNAs between control and OSCC samples. Quantitative real-time-polymerase chain reaction was employed to detect the expression of differentially expressed lncRNAs in human tongue squamous cell carcinoma and human oral keratinocytes cell lines. The biological function of lncRNA and its mechanism were examined via the experimental assessment of the cell lines with the lncRNA overexpressed and silenced. Additionally, to further explore the function of lncRNA in the progression of OSCC, xenograft tumour mouse models were established using 25 mice (5 groups, each with 5 mice). Tumour formation was observed at 2 weeks after the cell injection, and the tumours were resected at 5 weeks post-implantation. RESULTS Two lncRNAs, LINC00958 and AFAP1-AS1, were found to be correlated with the prognosis of OSCC. The results of the quantitative real-time-polymerase chain reaction indicated that the 2 lncRNAs were highly expressed in OSCC. In combination with the previous literature, we found AFAP1-AS1 to be a potentially important biomarker for OSCC. Thus, we further investigated its biological function and found that AFAP1-AS1 silencing inhibited cell proliferation, migration, and invasion whereas AFAP1-AS1 overexpression reversed the effect of AFAP1-AS1 silencing (P < .05). Mechanism analysis revealed that AFAP1-AS1 regulated the development of OSCC through the ubiquitin-mediated proteolysis pathway. CONCLUSIONS AFAP1-AS1 is an oncogene that aggravates the development of OSCC via the ubiquitin-mediated proteolysis pathway. It also provides a novel potential therapy for OSCC.
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Affiliation(s)
- Bao-Jun Li
- Department of Head and Neck Surgery, Harbin Medical University Cancer Hospital, Harbin, China
| | - Feng-Hai Ren
- Department of Thoracic Surgery, Harbin Medical University Cancer Hospital, Harbin, China
| | - Cui Zhang
- Department of Medical Ultrasound, Harbin Medical University Cancer Hospital, Harbin, China
| | - Xing-Wei Zhang
- Department of Oral and Maxillofacial Surgery, The First Affiliate Hospital of Harbin Medical University, Harbin, China
| | - Xiao-Hui Jiao
- Department of Oral and Maxillofacial Surgery, The First Affiliate Hospital of Harbin Medical University, Harbin, China.
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Zhao F, Xu D, Wang X, Wang X. FNDC5 affects invasion and migration of oral cancer by inhibiting PI3K/Akt/Snail signaling pathway. Sci Rep 2024; 14:26881. [PMID: 39505986 PMCID: PMC11542081 DOI: 10.1038/s41598-024-78391-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2024] [Accepted: 10/30/2024] [Indexed: 11/08/2024] Open
Abstract
This study first investigated how FNDC5 affected the development of oral cancer and revealed the role of FNDC5 in the migration and invasion of oral cancer. The present work evaluated differential FNDC5 expression within oral cancer samples versus matched non-carcinoma samples based on GEO database analysis and immunohistochemistry. We then generated oral cancer cell lines with FNDC5 overexpression and knockdown to determine the role of altered FNDC5 expression in the migration and invasion of oral cancer. PI3K inhibitor was used for investigating the possible mechanism underlying FNDC5 during EMT of oral cancer. Finally, these in-vitro results were validated using the lung metastatic nude mouse model. According to our results, FNDC5 level markedly decreased within oral cancer compared with adjacent samples and FNDC5 overexpression inhibited migration, invasion as well as EMT of oral cancer, while FNDC5 knockdown promoted oral cancer cell EMT. In addition, PI3K inhibitors blocked the induction of oral cancer cells EMT by FNDC5 knockdown. In vivo experiments further demonstrated the above results. This work is the first to illustrate the impact of FNDC5 on inhibiting migration and invasion of oral cancer, and our results suggest that FNDC5 affects EMT of oral cancer via the inhibition of PI3K/Akt/Snail pathway.
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Affiliation(s)
- Fang Zhao
- Department of Stomatology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Dongyang Xu
- Department of Stomatology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Xiumei Wang
- Department of Stomatology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
| | - Xiaofeng Wang
- Department of Stomatology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
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Jiang HM, Sun R, Ning BJ, Yang XQ, Zhu XJ. Acute severe hypokalemia caused by treatment of tongue squamous cell carcinoma with docetaxel and cisplatin: A case report. World J Clin Oncol 2024; 15:1309-1314. [DOI: 10.5306/wjco.v15.i10.1309] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2024] [Revised: 08/23/2024] [Accepted: 09/06/2024] [Indexed: 09/29/2024] Open
Abstract
BACKGROUND The tongue squamous cell carcinoma (TSCC) is an oral malignant tumor arising from the squamous epithelium of the tongue mucosa, characterized by a high malignant degree, invasive growth, early lymph node metastasis, and poor prognosis. Paclitaxel, represented by docetaxel, is now the standard first-line treatment for head and neck squamous cell carcinoma. Docetaxel, which belongs to the class of drugs known as paclitaxel, is an antitumor drug that inhibits cell mitosis and proliferation. Its adverse effects include myelosuppression, hair loss, gastrointestinal reactions, fluid retention, and allergic reactions. However, hypokalemia is rare, most cases are mild or moderate, and severe hypokalemia is seldom reported.
CASE SUMMARY During chemotherapy with docetaxel and cisplatin, a patient with TSCC developed severe hypokalemia. His potassium level was found to have been reduced to 1.85 mmol/L at the most critical situation. The patient had grade 1 muscle strength in all four limbs and could not perform any action, which was considered to be a sign of severe hypokalemia. Measures taken included intravenous infusion via micro-pump, intravenous injection, and oral potassium supplement, which gradually improved muscle strength and serum potassium levels. The patient survived the critical period of severe hypokalemia after chemotherapy. He was generally in good condition following treatment and discharged in stable condition.
CONCLUSION Docetaxel may cause severe hypokalemia with hypomagnesemia and the mechanism for this is not yet known to researchers yet. This means that nurses specializing in chemotherapy must exercise a high degree of responsibility, closely observe the patient’s reaction to the anticancer medication, notice any symptoms of adverse effects early. It is necessary to be considerate regarding individual differences between patients when selecting chemotherapy regimens and adhere to the principle of individualized treatment. Following multiple cycles of chemotherapy, patients should be aware of the accumulation of toxic side effects and receive blood tests reviewed within 24 hours of completion. It is essential to monitor electrolyte levels in patients suffering from severe gastrointestinal reactions to avoid complications that may result in death.
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Affiliation(s)
- Hong-Mei Jiang
- Department of Cancer Center, Daping Hospital, Army Medical University, Chongqing 400042, China
| | - Rong Sun
- Department of Cancer Center, Daping Hospital, Army Medical University, Chongqing 400042, China
| | - Bing-Jie Ning
- Department of Cancer Center, Daping Hospital, Army Medical University, Chongqing 400042, China
| | - Xue-Qin Yang
- Department of Cancer Center, Daping Hospital, Army Medical University, Chongqing 400042, China
| | - Xiao-Ju Zhu
- Department of Cancer Center, Daping Hospital, Army Medical University, Chongqing 400042, China
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Dong L, Xue L, Cheng W, Tang J, Ran J, Li Y. Comprehensive survival analysis of oral squamous cell carcinoma patients undergoing initial radical surgery. BMC Oral Health 2024; 24:919. [PMID: 39123139 PMCID: PMC11313127 DOI: 10.1186/s12903-024-04690-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2023] [Accepted: 07/30/2024] [Indexed: 08/12/2024] Open
Abstract
OBJECTIVE This study was designed to evaluate the five-year overall survival (OS) rate and postoperative survival time of patients diagnosed with oral squamous cell carcinoma (OSCC), as well as examine the clinical and pathological factors influencing survival outcomes in OSCC patients. METHODS Data were collected from OSCC patients who underwent their first radical surgical intervention in the Department of Maxillofacial Surgery at the First Affiliated Hospital of Chongqing Medical University between April 2014 and December 2016. Follow-up was conducted until March 2022. RESULTS The study included a total of 162 patients. The observed 5-year OS rate was 59.3%. Approximately 45.7% of OSCC patients experienced postoperative recurrence or metastasis, with a 5-year overall disease-free survival rate of 49.4%. There was no significant difference in the impact of sex, age, smoking, alcohol consumption, primary tumour location, depth of invasion or primary tumour size on the 5-year survival rate (p > 0.05). Univariate analysis revealed that clinical stage (Hazard Ratio = 2.239, p = 0.004), perineural invasion (PNI) (Hazard Ratio = 1.712, p = 0.03), lymph node metastasis (pN) (Hazard Ratio = 2.119, p = 0.002), pathological differentiation (Hazard Ratio = 2.715, p < 0.001), and recurrence or metastasis (Hazard Ratio = 10.02, p < 0.001) were significant factors influencing survival. Multivariate analysis further indicated that pathological differentiation (Hazard Ratio = 2.291, p = 0.001), PNI (Hazard Ratio = 1.765, p = 0.031) and recurrence or metastasis (Hazard Ratio = 9.256, p < 0.001) were independent risk factors of survival. Intriguingly, 11 OSCC patients were diagnosed with oesophageal squamous cell carcinoma (ESCC) within 1-4 years following surgery. CONCLUSION The survival prognosis of OSCC patients is significantly associated with clinical stage, PNI, lymph node metastasis, pathological differentiation, and recurrence or metastasis. Pathological differentiation, PNI and recurrence or metastasis are independent risk factors affecting survival. Routine clinical screening for ESCC may be recommended for OSCC patients with a history of alcohol consumption and tobacco use.
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Affiliation(s)
- Linsheng Dong
- Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Chongqing, 400016, P. R. China
- Chongqing Dental Hospital, Chongqing, 400010, P. R. China
| | - Lingli Xue
- Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Chongqing, 400016, P. R. China
| | - Wei Cheng
- Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Chongqing, 400016, P. R. China
| | - Jin Tang
- Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Chongqing, 400016, P. R. China
| | - Jingxuan Ran
- Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Chongqing, 400016, P. R. China
| | - Yadong Li
- Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Chongqing, 400016, P. R. China.
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Song F, Hou C, Huang Y, Liang J, Cai H, Tian G, Jiang Y, Wang Z, Hou J. Lactylome analyses suggest systematic lysine-lactylated substrates in oral squamous cell carcinoma under normoxia and hypoxia. Cell Signal 2024; 120:111228. [PMID: 38750680 DOI: 10.1016/j.cellsig.2024.111228] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2024] [Revised: 05/05/2024] [Accepted: 05/12/2024] [Indexed: 05/20/2024]
Abstract
Cancer cells tend to live in hypoxic environment characterized by enhanced glycolysis and accumulation of lactate. Intracellular lactate is shown to drive a novel type of post-translational modification (PTM), lysine lactylation (Kla). Kla has been confirmed to affect the malignant progression of tumors such as hepatocellular carcinoma (HCC) and colon cancer, whereas the global lactylomic profiling of oral squamous cell carcinoma (OSCC) is unclear. Here, the integrative lactylome and proteome analyses by using liquid chromatography-tandem mass spectrometry (LC-MS/MS) identified 1011 Kla sites within 532 proteins and 1197 Kla sites within 608 proteins in SCC25 cells under normoxic and hypoxic environments, respectively. Among these lactylated proteins, histones accounted for only a small fraction, suggesting the presence of Kla modification of OSCC in a large number of non-histone proteins. Notably, Kla preferred to enrich in spliceosome, ribosome and glycolysis/gluconeogenesis pathway in both normoxic and hypoxic cultures. Compared with normoxia, 589 differential proteins with 898 differentially lactylated sites were detected under hypoxia, which were mainly associated with the glycolysis/gluconeogenesis pathway by KEGG analysis. Importantly, we verified the presence of lactylation modification in the spliceosomal proteins hnRNPA1, SF3A1, hnRNPU and SLU7, as well as in glycolytic enzyme PFKP. In addition, the differential alternative splicing analysis described the divergence of pre-mRNA splicing patterns in the presence or absence of sodium lactate and at different oxygen concentrations. Finally, a negative correlation between tissue Kla levels and the prognosis of OSCC patients was revealed by immunohistochemistry. Our study is the first report to elucidate the lactylome and its biological function in OSCC, which deepens our understanding of the mechanisms underlying OSCC progression and provides a novel strategy for targeted therapy for OSCC.
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Affiliation(s)
- Fan Song
- Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong 510055, China; Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong 510055, China
| | - Chen Hou
- Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong 510055, China; Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong 510055, China
| | - Yingzhao Huang
- Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong 510055, China; Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong 510055, China
| | - Jianfeng Liang
- Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong 510055, China; Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong 510055, China
| | - Hongshi Cai
- Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong 510055, China; Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong 510055, China
| | - Guoli Tian
- Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong 510055, China; Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong 510055, China
| | - Yaoqi Jiang
- Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong 510055, China; Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong 510055, China
| | - Ziyi Wang
- Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong 510055, China; Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong 510055, China
| | - Jinsong Hou
- Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong 510055, China; Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong 510055, China.
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Mao C, Gong L, Kang W. Effect and mechanism of resveratrol on ferroptosis mediated by p53/SLC7A11 in oral squamous cell carcinoma. BMC Oral Health 2024; 24:773. [PMID: 38987730 PMCID: PMC11238462 DOI: 10.1186/s12903-024-04395-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2023] [Accepted: 05/21/2024] [Indexed: 07/12/2024] Open
Abstract
OBJECTIVE Resveratrol (Res) is a natural phytoestrogen with antitumor activity. This study sought to investigate the role of Res in ferroptosis in oral squamous cell carcinoma (OSCC). METHODS Normal human oral keratinocyte (HOK)/oral OSCC (CAL-27/SCC-9) cell lines were treated with different doses of Res. Res toxicity was determined by MTT assay, with half maximal inhibitory concentration values of Res on CAL-27 and SCC-9 cells calculated. Cell viability/colony formation efficiency/migration/invasion/cycle were assessed by CCK-8/colony formation assay/transwell assay/flow cytometry. The expression of p53 protein in the nucleus and cytoplasm, glutathione peroxidase 4 (GPX4) expression, and SLC7A11 messenger RNA (mRNA) and protein expression levels were determined by Western blot and RT-qPCR. Fe2+ content, reactive oxygen species (ROS) level, reduced glutathione (GSH), and lactate dehydrogenase (LDH) release were assessed. RESULTS Medium- to low-dose Res had no toxic effect on HOK cells, while high-dose Res markedly reduced HOK cell viability. Res significantly suppressed the viability of OSCC cells (CAL-27 and SCC-9). Res inhibited OSCC cell colony formation/migration/invasion, and induced G1 phase arrest. Res caused the translocation of p53 protein to the nucleus, obviously increased Fe2+ content, ROS level and LDH release, decreased GSH content and GPX4 protein expression, and induced ferroptosis. Down-regulation of p53 partially reversed the inhibitory effects of Res on CAL-27 cell malignant behaviors. Res inhibited SLC7A11 transcription by promoting p53 entry into the nucleus. SLC7A11 overexpression negated the the regulatory effects of p53 knockout on the role of Res in OSCC cell malignant behaviors and ferroptosis. CONCLUSION Res accelerated ferroptosis and inhibited malignant behaviors in OSCC cells by regulating p53/SLC7A11.
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Affiliation(s)
- Chen Mao
- Department of Stomatology, Loudi Central Hospital of Hunan Province, 51 Changqing Middle Street, Loudi, 417000, Hunan, China.
| | - Liqiang Gong
- Department of Stomatology, Loudi Central Hospital of Hunan Province, 51 Changqing Middle Street, Loudi, 417000, Hunan, China
| | - Wenming Kang
- Department of Stomatology, Loudi Central Hospital of Hunan Province, 51 Changqing Middle Street, Loudi, 417000, Hunan, China
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Kato M, Ota A, Ono T, Karnan S, Hyodo T, Rahman ML, Hasan MN, Onda M, Kondo S, Ito K, Furuhashi A, Hayashi T, Konishi H, Tsuzuki S, Hosokawa Y, Kazaoka Y. PDZ-binding kinase inhibitor OTS514 suppresses the proliferation of oral squamous carcinoma cells. Oral Dis 2024; 30:223-234. [PMID: 36799330 DOI: 10.1111/odi.14533] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Revised: 12/28/2022] [Accepted: 02/09/2023] [Indexed: 02/18/2023]
Abstract
OBJECTIVE PDZ-binding kinase (PBK) has been reported as a poor prognostic factor and is a promising molecular target for anticancer therapeutics. Here, we aimed to investigate the effect of specific PBK inhibitor OTS514 on the survival of OSCC cells. METHODS Four OSCC cell lines (HSC-2, HSC-3, SAS, and OSC-19) were used to examine the effect of OTS514 on cell survival and apoptosis. DNA microarray analysis was conducted to investigate the effect of OTS514 on gene expression in OSCC cells. Gene set enrichment analysis was performed to identify molecular signatures related to the antiproliferative effect of OTS514. RESULTS OTS514 decreased the cell survival of OSCC cells dose-dependently, and administration of OTS514 readily suppressed the HSC-2-derived tumor growth in immunodeficient mice. Treatment with OTS514 significantly increased the number of apoptotic cells and caspase-3/7 activity. Importantly, OTS514 suppressed the expression of E2F target genes with a marked decrease in protein levels of E2F1, a transcriptional factor. Moreover, TP53 knockdown attenuated OTS514-induced apoptosis. CONCLUSION OTS514 suppressed the proliferation of OSCC cells by downregulating the expression of E2F target genes and induced apoptosis by mediating the p53 signaling pathway. These results highlight the clinical application of PBK inhibitors in the development of molecular-targeted therapeutics against OSCC.
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Affiliation(s)
- Mikako Kato
- Department of Oral and Maxillofacial Surgery, Aichi Medical University Hospital, Nagakute, Japan
| | - Akinobu Ota
- Department of Biochemistry, Aichi Medical University School of Medicine, Nagakute, Japan
| | - Takayuki Ono
- Department of Oral and Maxillofacial Surgery, Aichi Medical University Hospital, Nagakute, Japan
| | - Sivasundaram Karnan
- Department of Biochemistry, Aichi Medical University School of Medicine, Nagakute, Japan
| | - Toshinori Hyodo
- Department of Biochemistry, Aichi Medical University School of Medicine, Nagakute, Japan
| | - Md Lutfur Rahman
- Department of Biochemistry, Aichi Medical University School of Medicine, Nagakute, Japan
| | - Muhammad Nazmul Hasan
- Department of Biochemistry, Aichi Medical University School of Medicine, Nagakute, Japan
| | - Maho Onda
- Department of Oral and Maxillofacial Surgery, Aichi Medical University Hospital, Nagakute, Japan
| | - Sayuri Kondo
- Department of Oral and Maxillofacial Surgery, Aichi Medical University Hospital, Nagakute, Japan
| | - Kunihiro Ito
- Department of Oral and Maxillofacial Surgery, Aichi Medical University Hospital, Nagakute, Japan
| | - Akifumi Furuhashi
- Department of Oral and Maxillofacial Surgery, Aichi Medical University Hospital, Nagakute, Japan
| | - Tomio Hayashi
- Department of Oral and Maxillofacial Surgery, Aichi Medical University Hospital, Nagakute, Japan
| | - Hiroyuki Konishi
- Department of Biochemistry, Aichi Medical University School of Medicine, Nagakute, Japan
| | - Shinobu Tsuzuki
- Department of Biochemistry, Aichi Medical University School of Medicine, Nagakute, Japan
| | - Yoshitaka Hosokawa
- Department of Biochemistry, Aichi Medical University School of Medicine, Nagakute, Japan
| | - Yoshiaki Kazaoka
- Department of Oral and Maxillofacial Surgery, Aichi Medical University Hospital, Nagakute, Japan
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11
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Zhang W, Lu R, Lv L, Ma C, Ding Y, Yang F, Fang Q, Wu Y, Pan R, Chen Y. 2α, 3α, 24-Thrihydroxyurs-12-en-24-ursolic acid enhances the cytotoxic effect of cisplatin on oral cancer cells by down-regulating autophagy. J Cell Biochem 2024; 125:e30504. [PMID: 37992225 DOI: 10.1002/jcb.30504] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Revised: 10/17/2023] [Accepted: 11/09/2023] [Indexed: 11/24/2023]
Abstract
This study aimed to investigate the effect and mechanism of 2α, 3α, 24-thrihydroxyurs-12-en-24-ursolic acid (TEOA) alone or in combination with cisplatin on oral cancer. TEOA, a pentacyclic triterpenoid compound isolated from the roots of Actinidia eriantha, has demonstrated antitumor activity in preclinical experiments. However, its role in oral cancer remains poorly understood. Our findings revealed that a low concentration of TEOA did not exhibit significant cytotoxicity against oral squamous cell carcinoma cells. However, when combined with cisplatin, TEOA showed a significant therapeutic effect. The combined treatments resulted in a significant inhibition of proliferation and migration and a significant increase in apoptosis of squamous cell carcinoma cells. Cisplatin exposure increased autophagy levels, which may contribute to chemoresistance. Of note, the presence of TEOA significantly inhibited cisplatin-induced autophagy, leading to improved chemotherapy efficacy. Our findings indicate that a mild low dosage of TEOA may enhance the cytotoxic effect of cisplatin by downregulating autophagy in oral cancer cells.
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Affiliation(s)
- Wentao Zhang
- Department of Stomatology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Cancer Center, Hangzhou, Zhejiang, China
| | - Ruijie Lu
- The Second Clinical Medical College, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Leyao Lv
- The Second Clinical Medical College, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Chenxi Ma
- The Second Clinical Medical College, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Yude Ding
- Department of Stomatology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Cancer Center, Hangzhou, Zhejiang, China
| | - Fan Yang
- Department of Stomatology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Cancer Center, Hangzhou, Zhejiang, China
| | - Qingxia Fang
- Department of Pharmacy, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Center for Clinical Pharmacy, Cancer Center, Hangzhou, Zhejiang, China
| | - Yue Wu
- Department of Pharmacy, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Center for Clinical Pharmacy, Cancer Center, Hangzhou, Zhejiang, China
| | - Ruolang Pan
- Institute for Cell-Based Drug Development of Zhejiang Province, S-Evans Biosciences, Hangzhou, China
- Key Laboratory of Cell-Based Drug and Applied Technology Development in Zhejiang Province, Hangzhou, China
| | - Yunfang Chen
- Department of Stomatology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Cancer Center, Hangzhou, Zhejiang, China
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12
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Liu Y, Wei C, Wang S, Ding S, Li Y, Li Y, Zhang D, Zhu G, Meng Z. Role of prognostic gene DKK1 in oral squamous cell carcinoma. Oncol Lett 2024; 27:52. [PMID: 38268623 PMCID: PMC10806357 DOI: 10.3892/ol.2023.14184] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Accepted: 10/25/2023] [Indexed: 01/26/2024] Open
Abstract
Oral squamous cell carcinoma (OSCC) is one of the most common squamous cell carcinomas of the head and neck. The morbidity and mortality rates of OSCC have increased in recent years. However, the pathogenesis of this disease remains unknown. The present study aimed to identify predictive biomarkers and therapeutic targets for OSCC. Bioinformatics screening of differentially expressed genes in OSCC was performed based on data from The Cancer Genome Atlas and Gene Expression Omnibus databases. Dickkopf Wnt signaling pathway inhibitor 1 (DKK1) was identified to be associated with survival, tumor immunity and DNA repair in OSCC. Furthermore, the effects of DKK1 were evaluated by the knockdown of DKK1 in two OSCC cell lines. The proliferation, clonogenicity, migration and invasion of the cells were assessed in vitro using Cell Counting Kit-8, colony formation, wound healing and Transwell assays, respectively, and were found to be inhibited by DKK1 knockdown. The present study suggests that DKK1 may be used in the prognosis of patients with OSCC and that targeting DKK1 is a potential strategy for OSCC therapy.
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Affiliation(s)
- Yujiao Liu
- Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Shandong University and Shandong Provincial Key Laboratory of Oral Tissue Regeneration and Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, Shandong 250000, P.R. China
- Department of Stomatology & Precision Biomedical Laboratory, Liaocheng People's Hospital, Liaocheng University, Liaocheng, Shandong 252000, P.R. China
| | - Congcong Wei
- Department of Stomatology & Precision Biomedical Laboratory, Liaocheng People's Hospital, Liaocheng University, Liaocheng, Shandong 252000, P.R. China
| | - Song Wang
- Department of Stomatology & Precision Biomedical Laboratory, Liaocheng People's Hospital, Liaocheng University, Liaocheng, Shandong 252000, P.R. China
| | - Shuxin Ding
- School of Stomatology, Weifang Medical University, Weifang, Shandong 261000, P.R. China
| | - Yanan Li
- Biomedical Laboratory, Medical School of Liaocheng University, Liaocheng, Shandong 252000, P.R. China
| | - Yongguo Li
- Department of Stomatology & Precision Biomedical Laboratory, Liaocheng People's Hospital, Liaocheng University, Liaocheng, Shandong 252000, P.R. China
| | - Dongping Zhang
- Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Shandong University and Shandong Provincial Key Laboratory of Oral Tissue Regeneration and Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, Shandong 250000, P.R. China
- Department of Stomatology & Precision Biomedical Laboratory, Liaocheng People's Hospital, Liaocheng University, Liaocheng, Shandong 252000, P.R. China
| | - Guoxiong Zhu
- Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Shandong University and Shandong Provincial Key Laboratory of Oral Tissue Regeneration and Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, Shandong 250000, P.R. China
- Department of Stomatology, PLA 960th Hospital, Jinan, Shandong 250000, P.R. China
| | - Zhen Meng
- Department of Stomatology & Precision Biomedical Laboratory, Liaocheng People's Hospital, Liaocheng University, Liaocheng, Shandong 252000, P.R. China
- Biomedical Laboratory, Medical School of Liaocheng University, Liaocheng, Shandong 252000, P.R. China
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13
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Lv T, Liu H, Mao L, Song Y, Liao L, Zhong K, Shuai B, Luo Y, Guo T, Huang W, Zhang S. Cancer-associated fibroblast-derived extracellular vesicles promote lymph node metastases in oral cavity squamous cell carcinoma by encapsulating ITGB1 and BMI1. BMC Cancer 2024; 24:113. [PMID: 38254031 PMCID: PMC10804601 DOI: 10.1186/s12885-024-11855-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2023] [Accepted: 01/07/2024] [Indexed: 01/24/2024] Open
Abstract
BACKGROUND Extracellular vesicles (EVs) have been revealed to facilitate the development of oral squamous cavity cell carcinoma (OCSCC), while its supporting role in lymph node metastases is under continuous investigation. This study aimed to examine the function of cancer-associated fibroblasts (CAF)-derived EVs (CAF-EVs) during lymph node metastasis in OCSCC and the mechanisms. METHODS CAF were isolated from OCSCC tissues of patients, and CAF-EVs were extracted and identified. EdU, colony formation, wound healing, and Transwell assays were performed. The OCSCC cells before and after CAF-EVs treatment were injected into mice to probe the effects of CAF-EVs on tumor growth and lymph node metastasis, respectively. The effect of CAF-EVs treatment on transcriptome changes in OCSCC cells was analyzed. Clinical data of patients with OCSCC were analyzed to determine the prognostic significance of the selected genes. Finally, loss-of-function assays were conducted to corroborate the involvement of polycomb complex protein BMI-1 (BMI1) and integrin beta1 (ITGB1). RESULTS CAF-EVs promoted the malignant behavior of OCSCC cells and accelerated tumor growth and lymph node metastasis in mice. CAF-EVs significantly increased the expression of BMI1 and ITGB1, and the expression of BMI1 and ITGB1 was negatively correlated with the overall survival and relapse-free survival of OCSCC patients. Knockdown of BMI1 or ITGB1 in OCSCC cells abated the promoting effects of CAF-EVs in vitro and in vivo. CONCLUSION CAF-EVs elicited the metastasis-promoting properties in OCSCC by elevating BMI1 and ITGB1, suggesting that BMI1 and ITGB1 could be potential biomarkers and therapeutic targets for OCSCC.
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Affiliation(s)
- Tianzhu Lv
- Guizhou Medical University, 550004, Guiyang, Guizhou, P.R. China
- China-British Joint Molecular Head and Neck Cancer Research Laboratory, Stomatological Hospital of Guizhou Medical University, 550004, Guiyang, Guizhou, P.R. China
| | - Hongjing Liu
- Comprehensive Emergency Department of Stomatology, Stomatological Hospital of Guizhou Medical University, 550004, Guiyang, Guizhou, P.R. China
| | - Ling Mao
- Guizhou Medical University, 550004, Guiyang, Guizhou, P.R. China
- China-British Joint Molecular Head and Neck Cancer Research Laboratory, Stomatological Hospital of Guizhou Medical University, 550004, Guiyang, Guizhou, P.R. China
| | - Yanrong Song
- Comprehensive Emergency Department of Stomatology, Stomatological Hospital of Guizhou Medical University, 550004, Guiyang, Guizhou, P.R. China
| | - Lili Liao
- Comprehensive Emergency Department of Stomatology, Stomatological Hospital of Guizhou Medical University, 550004, Guiyang, Guizhou, P.R. China
| | - Kun Zhong
- Comprehensive Emergency Department of Stomatology, Stomatological Hospital of Guizhou Medical University, 550004, Guiyang, Guizhou, P.R. China
| | - Binbin Shuai
- Comprehensive Emergency Department of Stomatology, Stomatological Hospital of Guizhou Medical University, 550004, Guiyang, Guizhou, P.R. China
| | - Yingkun Luo
- Comprehensive Emergency Department of Stomatology, Stomatological Hospital of Guizhou Medical University, 550004, Guiyang, Guizhou, P.R. China
| | - Tingting Guo
- Comprehensive Emergency Department of Stomatology, Stomatological Hospital of Guizhou Medical University, 550004, Guiyang, Guizhou, P.R. China
| | - Wentao Huang
- School of Savaid Stomatology, Hangzhou Medical College, 311399, Hangzhou, Zhejiang, P.R. China.
| | - Shenyingjie Zhang
- Medical Department, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), 310006, Hangzhou, Zhejiang, P.R. China
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14
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Yang Z, He F. An immune cell infiltration landscape classification to predict prognosis and immunotherapy effect in oral squamous cell carcinoma. Comput Methods Biomech Biomed Engin 2024; 27:191-203. [PMID: 36794748 DOI: 10.1080/10255842.2023.2179364] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2022] [Accepted: 02/07/2023] [Indexed: 02/17/2023]
Abstract
Tumor immune cell infiltration (ICI) is associated with the prognosis of oral squamous cell carcinoma (OSCC) patients and the effect of immunotherapy. The combat algorithm was used to merge the data from three databases and the Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) algorithm to quantify the amount of infiltrated immune cells. Unsupervised consistent cluster analysis was used to determine ICI subtypes, and differentially expressed genes (DEGs) were determined according to these subtypes. The DEGs were then clustered again to obtain the ICI gene subtypes. The principal component analysis (PCA) and the Boruta algorithm were used to construct the ICI scores. Three different ICI clusters and gene clusters with a prognosis of significant difference were found and the ICI score was constructed. Patients with higher ICI scores have a better prognosis following internal and external verification. Besides, the proportion of patients with effective immunotherapy was higher than those with low scores in two external datasets with immunotherapy. This study shows that the ICI score is an effective prognostic biomarker and a predictor of immunotherapy.
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Affiliation(s)
- Zhiqiang Yang
- Department of Stomatology, Meishan People's Hospital, Meishan, China
| | - Fan He
- Department of Stomatology, Meishan People's Hospital, Meishan, China
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15
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Ren J, Jing X, Liu Y, Liu J, Ning X, Zong M, Zhang R, Cheng H, Cui J, Li B, Wu X. Exosome-based engineering strategies for the diagnosis and treatment of oral and maxillofacial diseases. J Nanobiotechnology 2023; 21:501. [PMID: 38129853 PMCID: PMC10740249 DOI: 10.1186/s12951-023-02277-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2023] [Accepted: 12/15/2023] [Indexed: 12/23/2023] Open
Abstract
Oral and maxillofacial diseases are one of the most prevalent diseases in the world, which not only seriously affect the health of patients' oral and maxillofacial tissues, but also bring serious economic and psychological burdens to patients. Therefore, oral and maxillofacial diseases require effective treatment. Traditional treatments have limited effects. In recent years, nature exosomes have attracted increasing attention due to their ability to diagnose and treat diseases. However, the application of nature exosomes is limited due to low yield, high impurities, lack of targeting, and high cost. Engineered exosomes can be endowed with better comprehensive therapeutic properties by modifying exosomes of parent cells or directly modifying exosomes, and biomaterial loading exosomes. Compared with natural exosomes, these engineered exosomes can achieve more effective diagnosis and treatment of oral and maxillary system diseases, and provide reference and guidance for clinical application. This paper reviews the engineering modification methods of exosomes and the application of engineered exosomes in oral and maxillofacial diseases and looks forward to future research directions.
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Affiliation(s)
- Jianing Ren
- Shanxi Medical University School and Hospital of Stomatology, Taiyuan, 030001, Shanxi, China
- Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Taiyuan, 030001, Shanxi, China
| | - Xuan Jing
- Shanxi Medical University School and Hospital of Stomatology, Taiyuan, 030001, Shanxi, China
- Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Taiyuan, 030001, Shanxi, China
| | - Yingyu Liu
- Shanxi Medical University School and Hospital of Stomatology, Taiyuan, 030001, Shanxi, China
- Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Taiyuan, 030001, Shanxi, China
| | - Jinrong Liu
- Shanxi Medical University School and Hospital of Stomatology, Taiyuan, 030001, Shanxi, China
- Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Taiyuan, 030001, Shanxi, China
| | - Xiao Ning
- Shanxi Medical University School and Hospital of Stomatology, Taiyuan, 030001, Shanxi, China
- Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Taiyuan, 030001, Shanxi, China
| | - Mingrui Zong
- Shanxi Medical University School and Hospital of Stomatology, Taiyuan, 030001, Shanxi, China
- Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Taiyuan, 030001, Shanxi, China
| | - Ran Zhang
- Shanxi Medical University School and Hospital of Stomatology, Taiyuan, 030001, Shanxi, China
- Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Taiyuan, 030001, Shanxi, China
| | - Huaiyi Cheng
- Shanxi Medical University School and Hospital of Stomatology, Taiyuan, 030001, Shanxi, China
- Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Taiyuan, 030001, Shanxi, China
| | - Jiayu Cui
- Shanxi Medical University School and Hospital of Stomatology, Taiyuan, 030001, Shanxi, China
- Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Taiyuan, 030001, Shanxi, China
| | - Bing Li
- Shanxi Medical University School and Hospital of Stomatology, Taiyuan, 030001, Shanxi, China.
- Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Taiyuan, 030001, Shanxi, China.
| | - Xiuping Wu
- Shanxi Medical University School and Hospital of Stomatology, Taiyuan, 030001, Shanxi, China.
- Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Taiyuan, 030001, Shanxi, China.
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16
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Shi E, Shan T, Wang H, Mao L, Liang Y, Cao M, Wu Q, Li C, Wang Y, Wang Y. A Bacterial Nanomedicine Combines Photodynamic-Immunotherapy and Chemotherapy for Enhanced Treatment of Oral Squamous Cell Carcinoma. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2023; 19:e2304014. [PMID: 37653616 DOI: 10.1002/smll.202304014] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/12/2023] [Revised: 08/08/2023] [Indexed: 09/02/2023]
Abstract
Bacterial therapy is an emerging hotspot in tumor immunotherapy, which can initiate antitumor immune activation through multiple mechanisms. Porphyromonas gingivalis (Pg), a pathogenic bacterium inhabiting the oral cavity, contains a great deal of pathogen associated molecular patterns that can activate various innate immune cells to promote antitumor immunity. Owing to the presence of protoporphyrin IX (PpIX), Pg is also an excellent photosensitizer for photodynamic therapy (PDT) via the in situ generation of reactive oxygen species. This study reports a bacterial nanomedicine (nmPg) fabricated from Pg through lysozyme degradation, ammonium chloride lysis, and nanoextrusion, which has potent PDT and immune activation performances for oral squamous cell carcinoma (OSCC) treatment. To further promote the tumoricidal efficacy, a commonly used chemotherapeutic drug doxorubicin (DOX) is efficiently encapsulated into nmPg through a simple incubation method. nmPg/DOX thus prepared exhibits significant synergistic effects on inhibiting the growth and metastasis of OSCC both in vitro and in vivo via photodynamic-immunotherapy and chemotherapy. In summary, this work develops a promising bacterial nanomedicine for enhanced treatment of OSCC.
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Affiliation(s)
- Enyu Shi
- School and Hospital of Stomatology, Tianjin Medical University, Tianjin, 300070, China
| | - Tianhe Shan
- Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin, 300070, China
| | - Hanping Wang
- School and Hospital of Stomatology, Tianjin Medical University, Tianjin, 300070, China
| | - Lujia Mao
- School and Hospital of Stomatology, Tianjin Medical University, Tianjin, 300070, China
| | - Yanjie Liang
- School and Hospital of Stomatology, Tianjin Medical University, Tianjin, 300070, China
| | - Mingxin Cao
- School and Hospital of Stomatology, Tianjin Medical University, Tianjin, 300070, China
| | - Qiqi Wu
- School and Hospital of Stomatology, Tianjin Medical University, Tianjin, 300070, China
| | - Changyi Li
- School and Hospital of Stomatology, Tianjin Medical University, Tianjin, 300070, China
| | - Yue Wang
- School and Hospital of Stomatology, Tianjin Medical University, Tianjin, 300070, China
| | - Yinsong Wang
- School and Hospital of Stomatology, Tianjin Medical University, Tianjin, 300070, China
- Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin, 300070, China
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17
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Huang K, Liu Z, Kim MO, Kim KR. Anticancer effects of gossypetin from Hibiscus sabdariffa in oral squamous cell carcinoma. J Appl Oral Sci 2023; 31:e20230243. [PMID: 37820185 PMCID: PMC10561964 DOI: 10.1590/1678-7757-2023-0243] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Revised: 08/17/2023] [Accepted: 08/21/2023] [Indexed: 10/13/2023] Open
Abstract
OBJECTIVE Gossypetin, isolated from Hibiscus sabdariffa L, has been shown to have various pharmacological effects including anti-inflammatory and antibacterial activity against various diseases. However, since the effect of gossypetin in oral cancer remains to be reported, we aimed to investigate the anticancer activity and mechanisms of gossypetin in oral squamous cell carcinoma (OSCC). METHODOLOGY The proliferation of OSCC cells was evaluated by cell viability and soft agar colony assays. The effects of gossypetin on the migration and invasion of OSCC cells was investigated by wound healing and transwell invasion assays, respectively. Apoptosis and cell cycle arrest were measured by flow cytometry. Moreover, the anticancer mechanism of gossypetin in OSCC cells was analyzed by western blotting. RESULTS Gossypetin inhibited the proliferation, migration, and invasion of OSCC cells and induced apoptosis by upregulating the Bax/Bcl-2 ratio and cell cycle arrest at the G2/M phase. Furthermore, gossypetin regulated the activation of extracellular signal-regulated kinase and nuclear factor-kappa B. CONCLUSION Results showed that gossypetin inhibits the proliferation, migration, and invasion of OSCC cells and triggers apoptosis and cell cycle arrest in OSCC. Therefore, gossypetin has the potential for use as a chemopreventive agent in oral cancer.
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Affiliation(s)
- Ke Huang
- Kyungpook National University, Graduate School of Science and Technology, Department of Dental Hygiene, Sangju 37224, Republic of Korea
- Kyungpook National University, Research Center for Horse Industry, Department of Animal Science and Biotechnology, Sangju 37224, Republic of Korea
| | - Zhibin Liu
- Kyungpook National University, Graduate School of Science and Technology, Department of Dental Hygiene, Sangju 37224, Republic of Korea
- Kyungpook National University, Research Center for Horse Industry, Department of Animal Science and Biotechnology, Sangju 37224, Republic of Korea
| | - Myoung-Ok Kim
- Kyungpook National University, Research Center for Horse Industry, Department of Animal Science and Biotechnology, Sangju 37224, Republic of Korea
| | - Ki-Rim Kim
- Kyungpook National University, Graduate School of Science and Technology, Department of Dental Hygiene, Sangju 37224, Republic of Korea
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18
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Murakami A, Takeda D, Hirota J, Saito I, Amano-Iga R, Yatagai N, Arimoto S, Kakei Y, Akashi M, Hasegawa T. Relationship of Mitochondrial-Related Protein Expression with the Differentiation, Metastasis, and Poor Prognosis of Oral Squamous Cell Carcinoma. Cancers (Basel) 2023; 15:4071. [PMID: 37627097 PMCID: PMC10452162 DOI: 10.3390/cancers15164071] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2023] [Revised: 08/09/2023] [Accepted: 08/09/2023] [Indexed: 08/27/2023] Open
Abstract
Mitochondrial dysfunction and respiratory function changes have been consistently associated with the initiation and progression of cancer. The purpose of this study was to retrospectively investigate the expression of mitochondrial tumor-suppressor and DNA-repair proteins in patients with oral squamous cell carcinoma (OSCC) and to evaluate the relationship between their expression and prognosis. We enrolled 197 patients with OSCC who underwent surgical resection between August 2013 and October 2018. Clinical, pathological, and epidemiological data were retrospectively collected from hospital records. The expression of peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), mitochondrial transcription factor A, mitochondrial tumor suppressor gene 1, silent information regulator 3, and 8-hydroxyguanine DNA glycosylase was investigated using immunochemistry. The 3-year disease-specific survival (DSS) rates of patients showing positive expression of all selected proteins were significantly higher than those of patients showing a lack of expression. Multivariate analysis revealed that the expression of PGC-1α (hazard ratio, 4.684) and vascular invasion (hazard ratio, 5.690) can predict the DSS rate (p < 0.001). Low PGC-1α expression and vascular invasion are potential clinically effective predictors of the prognosis of OSCC.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | - Takumi Hasegawa
- Department of Oral and Maxillofacial Surgery, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan; (A.M.); (D.T.); (S.A.); (Y.K.); (M.A.)
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19
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Gambino A, Martina E, Panzarella V, Ruggiero T, Haddad GE, Broccoletti R, Arduino PG. Potential use of optical coherence tomography in oral potentially malignant disorders: in-vivo case series study. BMC Oral Health 2023; 23:540. [PMID: 37542232 PMCID: PMC10403886 DOI: 10.1186/s12903-023-03263-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2023] [Accepted: 07/28/2023] [Indexed: 08/06/2023] Open
Abstract
BACKGROUND Evidence confirms that the use of Optical Coherence Tomography (OCT) in oral medicine can be a reliable aid for the diagnosis and management of Oral Potentially Malignant Disorders (OPMDs). Several authors described the ability of this system to detect the structural changes of the epithelia involved by the OPMDs. The purpose of this case series is to provide a suggestion for interpretation of OCT images from different OPMDs, compared to OCT images of healthy tissues. METHODS A sample of 11 OPMDs patients was recruited and analyzed with OCT. The images obtained were then compared with an OCT repertoire image. In this work the reflectance degree was considered, together with the analysis of the increased/decreased thicknesses of the various layers. Keratin Layer (KL), Epithelial Layer (EP), Lamina Propria (LP), Basal Membrane (BM) assessment, for each lesion, was performed. RESULTS OCT measurements of KL, EP and LP layers, together with BM assessing, should aid the physicians to recognize and describe different oral lesions, relating them to the corresponding oral pathology. CONCLUSION More studies like this, on larger samples, are needed to validate the results and provide, in the future, a kind of manual that could guide clinicians to correctly interpret the OCT images in relation to the causing pathologies. TRIAL REGISTRATION The present trial has been registered with ISRCTN (#17,893,224).
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Affiliation(s)
- Alessio Gambino
- Department of Surgical Sciences, CIR Dental School, University of Turin, Via Nizzan.230, 10123, Turin, Italy.
| | - Eugenio Martina
- Department of Surgical Sciences, CIR Dental School, University of Turin, Via Nizzan.230, 10123, Turin, Italy
| | - Vera Panzarella
- Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy
| | - Tiziana Ruggiero
- Department of Surgical Sciences, CIR Dental School, University of Turin, Via Nizzan.230, 10123, Turin, Italy
| | - Giorgia El Haddad
- Department of Surgical Sciences, CIR Dental School, University of Turin, Via Nizzan.230, 10123, Turin, Italy
| | - Roberto Broccoletti
- Department of Surgical Sciences, CIR Dental School, University of Turin, Via Nizzan.230, 10123, Turin, Italy
| | - Paolo G Arduino
- Department of Surgical Sciences, CIR Dental School, University of Turin, Via Nizzan.230, 10123, Turin, Italy
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20
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Li L, Chen L, Li Z, Huang S, Chen Y, Li Z, Chen W. FSCN1 promotes proliferation, invasion and glycolysis via the IRF4/AKT signaling pathway in oral squamous cell carcinoma. BMC Oral Health 2023; 23:519. [PMID: 37491232 PMCID: PMC10369755 DOI: 10.1186/s12903-023-03191-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Accepted: 06/30/2023] [Indexed: 07/27/2023] Open
Abstract
BACKGROUND Oral squamous cell carcinoma (OSCC) is a disease with increasing incidence worldwide that leads to deformity and death. In OSCC, fascin actin-bundling protein 1 (FSCN1) is an oncogene involved in the tumorigenesis process. However, the functions and potential mechanisms of FSCN1 in the OSCC tumorigenesis process have not been reported thus far. METHODS We used qRT‒PCR to detect the expression of FSCN1 in 40 paired OSCC tumor tissues (tumor) and neighboring noncancerous tissues. The role of FSCN1 was also assessed in vitro through colony formation, CCK-8, and transwell assays. Moreover, glucose consumption was detected. Western blotting was used to confirm the interaction of FSCN1, IRF4 and AKT. RESULTS FSCN1 was remarkably overexpressed in OSCC tissues and cell lines compared to corresponding controls. In addition, colony formation, CCK-8, and transwell assays revealed a notable reduction in OSCC growth and invasion when FSCN1 was silenced. FSCN1 silencing remarkably suppressed OSCC glycolysis. Mechanistic studies showed that FSCN1 achieves its function partially by activating interferon regulatory factor 4 (IRF4) and the AKT pathway in OSCC. CONCLUSION In conclusion, our study investigated the functions and mechanisms of the FSCN1/IRF4/AKT pathway in OSCC progression. In OSCC, FSCN1 is likely to be a biomarker and therapeutic target.
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Affiliation(s)
- Liang Li
- Department of Stomatology, the First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, 510080, China
| | - Lihui Chen
- State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China
| | - Zhangwei Li
- Department of Stomatology, the First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, 510080, China
| | - Shiqin Huang
- State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China
| | - Yaoyao Chen
- State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China
| | - Zhiyong Li
- State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China.
| | - Wenkuan Chen
- State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China.
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21
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Machado TQ, Lima MED, da Silva RC, Macedo AL, de Queiroz LN, Angrisani BRP, da Fonseca ACC, Câmara PR, Rabelo VVH, Carollo CA, de Lima Moreira D, de Almeida ECP, Vasconcelos TRA, Abreu PA, Valverde AL, Robbs BK. Anticancer Activity and Molecular Targets of Piper cernuum Substances in Oral Squamous Cell Carcinoma Models. Biomedicines 2023; 11:1914. [PMID: 37509552 PMCID: PMC10377665 DOI: 10.3390/biomedicines11071914] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2023] [Revised: 06/29/2023] [Accepted: 06/30/2023] [Indexed: 07/30/2023] Open
Abstract
Oral squamous cell carcinoma (OSCC) is a worldwide public health problem, with high morbidity and mortality rates. The development of new drugs to treat OSCC is paramount. Piper plant species have shown many biological activities. In the present study, we show that dichloromethane partition of Piper cernuum (PCLd) is nontoxic in chronic treatment in mice, reduces the amount of atypia in tongues of chemically induced OSCC, and significantly increases animal survival. To identify the main active compounds, chromatographic purification of PCLd was performed, where fractions 09.07 and 14.05 were the most active and selective. These fractions promoted cell death by apoptosis characterized by phosphatidyl serine exposition, DNA fragmentation, and activation of effector caspase-3/7 and were nonhemolytic. LC-DAD-MS/MS analysis did not propose matching spectra for the 09.07 fraction, suggesting compounds not yet known. However, aporphine alkaloids were annotated in fraction 14.05, which are being described for the first time in P. cernuum and corroborate the observed cytotoxic activity. Putative molecular targets were determined for these alkaloids, in silico, where the androgen receptor (AR), CHK1, CK2, DYRK1A, EHMT2, LXRβ, and VEGFR2 were the most relevant. The results obtained from P. cernuum fractions point to promising compounds as new preclinical anticancer candidates.
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Affiliation(s)
- Thaíssa Queiróz Machado
- Postgraduate Program in Applied Science for Health Products, Faculty of Pharmacy, Fluminense Federal University, Niteroi 24241-000, RJ, Brazil
| | - Maria Emanuelle Damazio Lima
- Department of Organic Chemistry, Chemistry Institute, Fluminense Federal University, Niteroi 24020-141, RJ, Brazil
| | - Rafael Carriello da Silva
- Postgraduate Program in Dentistry, Health Institute of Nova Friburgo, Fluminense Federal University, Nova Friburgo 28625-650, RJ, Brazil
| | - Arthur Ladeira Macedo
- Pharmaceutical Sciences, Food and Nutrition Faculty, Mato Grosso do Sul Federal University, Campo Grande 79070-900, MS, Brazil
| | - Lucas Nicolau de Queiroz
- Postgraduate Program in Applied Science for Health Products, Faculty of Pharmacy, Fluminense Federal University, Niteroi 24241-000, RJ, Brazil
| | | | - Anna Carolina Carvalho da Fonseca
- Postgraduate Program in Dentistry, Health Institute of Nova Friburgo, Fluminense Federal University, Nova Friburgo 28625-650, RJ, Brazil
| | - Priscilla Rodrigues Câmara
- Basic Science Department, Health Institute of Nova Friburgo, Fluminense Federal University, Nova Friburgo 28625-650, RJ, Brazil
| | - Vitor Von-Held Rabelo
- Biodiversity and Sustainability Institute, Macaé Campus, Federal University of Rio de Janeiro, Macae 21941-901, RJ, Brazil
| | - Carlos Alexandre Carollo
- Pharmaceutical Sciences, Food and Nutrition Faculty, Mato Grosso do Sul Federal University, Campo Grande 79070-900, MS, Brazil
| | - Davyson de Lima Moreira
- Research Directorate, Laboratory of Natural Products and Biochemistry, Rio de Janeiro Botanical Garden Research Institute, Rio de Janeiro 22460-030, RJ, Brazil
| | - Elan Cardozo Paes de Almeida
- Basic Science Department, Health Institute of Nova Friburgo, Fluminense Federal University, Nova Friburgo 28625-650, RJ, Brazil
| | | | - Paula Alvarez Abreu
- Biodiversity and Sustainability Institute, Macaé Campus, Federal University of Rio de Janeiro, Macae 21941-901, RJ, Brazil
| | - Alessandra Leda Valverde
- Department of Organic Chemistry, Chemistry Institute, Fluminense Federal University, Niteroi 24020-141, RJ, Brazil
| | - Bruno Kaufmann Robbs
- Basic Science Department, Health Institute of Nova Friburgo, Fluminense Federal University, Nova Friburgo 28625-650, RJ, Brazil
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22
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Silva JPN, Pinto B, Monteiro L, Silva PMA, Bousbaa H. Combination Therapy as a Promising Way to Fight Oral Cancer. Pharmaceutics 2023; 15:1653. [PMID: 37376101 PMCID: PMC10301495 DOI: 10.3390/pharmaceutics15061653] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2023] [Revised: 05/30/2023] [Accepted: 05/30/2023] [Indexed: 06/29/2023] Open
Abstract
Oral cancer is a highly aggressive tumor with invasive properties that can lead to metastasis and high mortality rates. Conventional treatment strategies, such as surgery, chemotherapy, and radiation therapy, alone or in combination, are associated with significant side effects. Currently, combination therapy has become the standard practice for the treatment of locally advanced oral cancer, emerging as an effective approach in improving outcomes. In this review, we present an in-depth analysis of the current advancements in combination therapies for oral cancer. The review explores the current therapeutic options and highlights the limitations of monotherapy approaches. It then focuses on combinatorial approaches that target microtubules, as well as various signaling pathway components implicated in oral cancer progression, namely, DNA repair players, the epidermal growth factor receptor, cyclin-dependent kinases, epigenetic readers, and immune checkpoint proteins. The review discusses the rationale behind combining different agents and examines the preclinical and clinical evidence supporting the effectiveness of these combinations, emphasizing their ability to enhance treatment response and overcome drug resistance. Challenges and limitations associated with combination therapy are discussed, including potential toxicity and the need for personalized treatment approaches. A future perspective is also provided to highlight the existing challenges and possible resolutions toward the clinical translation of current oral cancer therapies.
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Affiliation(s)
- João P. N. Silva
- UNIPRO—Oral Pathology and Rehabilitation Research Unit, University Institute of Health Sciences (IUCS), Cooperativa de Ensino Superior Politécnico e Universitário (CESPU), Rua Central de Gandra, 1317, 4585-116 Gandra, Portugal; (J.P.N.S.); (B.P.); (L.M.)
| | - Bárbara Pinto
- UNIPRO—Oral Pathology and Rehabilitation Research Unit, University Institute of Health Sciences (IUCS), Cooperativa de Ensino Superior Politécnico e Universitário (CESPU), Rua Central de Gandra, 1317, 4585-116 Gandra, Portugal; (J.P.N.S.); (B.P.); (L.M.)
| | - Luís Monteiro
- UNIPRO—Oral Pathology and Rehabilitation Research Unit, University Institute of Health Sciences (IUCS), Cooperativa de Ensino Superior Politécnico e Universitário (CESPU), Rua Central de Gandra, 1317, 4585-116 Gandra, Portugal; (J.P.N.S.); (B.P.); (L.M.)
| | - Patrícia M. A. Silva
- UNIPRO—Oral Pathology and Rehabilitation Research Unit, University Institute of Health Sciences (IUCS), Cooperativa de Ensino Superior Politécnico e Universitário (CESPU), Rua Central de Gandra, 1317, 4585-116 Gandra, Portugal; (J.P.N.S.); (B.P.); (L.M.)
- TOXRUN—Toxicology Research Unit, University Institute of Health Sciences (IUCS), Cooperativa de Ensino Superior Politécnico e Universitário (CESPU), Rua Central de Gandra, 1317, 4585-116 Gandra, Portugal
| | - Hassan Bousbaa
- UNIPRO—Oral Pathology and Rehabilitation Research Unit, University Institute of Health Sciences (IUCS), Cooperativa de Ensino Superior Politécnico e Universitário (CESPU), Rua Central de Gandra, 1317, 4585-116 Gandra, Portugal; (J.P.N.S.); (B.P.); (L.M.)
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Du Y, Shuai Y, Wang H, Li H, Li Y. Exosome-mediated long noncoding RNA (lncRNA) PART1 suppresses malignant progression of oral squamous cell carcinoma via miR-17-5p/SOCS6 axis. Turk J Med Sci 2023; 53:630-639. [PMID: 37476905 PMCID: PMC10388088 DOI: 10.55730/1300-0144.5625] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2022] [Accepted: 01/17/2023] [Indexed: 07/22/2023] Open
Abstract
BACKGROUND Exosomes derived from oral squamous cell carcinoma (OSCC) could modulate OSCC development. This study aimed to explore effects of exosome-mediated lncRNA PART1 on OSCC cells. METHODS This study was performed in Tianjin Medical University Cancer Institute from February 2021 to March 2022. Bioinformatic analysis was performed on the public database GEPIA (http://gepia.cancer-pku.cn/). Exosomes isolated from cell lines squamous cell carcinoma 9 (SCC9) and Centre Antoine Lacassagne-27 (CAL27) were identified by transmission electron microscope and western blot. Exosome-mediated lncRNA PART1, microRNA-17-5p(miR-17-5p) and suppressor of cytokine signaling 6(SOCS6) RNA expressions were assessed by quantitative reverse transcription polymerase chain reaction (RT-qPCR). Cell counting kit8(CCK-8), caspase-3 activity, and flow cytometry were applied to evaluate OSCC cell viabilities and apoptosis. Meanwhile, OSCC cell migratory ability and invasiveness were evaluated using transwell assay. Bindings between miR-17-5p and lncRNA PART1 or SOCS6 were validated using the luciferase reporter test. Western blot was used for detecting the protein levels of SOCS6, phosphorylated signal transducer and activator of transcription 3 (STAT3) and STAT3. RESULTS : According to GEPIA, lncRNA PART1 was downregulated in OSCC tissue samples and cells, and it had a positive correlation with the good prognosis of Head and neck squamous cell cancer (HNSCC) patients. After the exosomes from OSCC cells were isolated and verified, PART1 was then confirmed to be secreted by exosomes. Further, overexpression of exosome-mediated lncRNA PART1 inhibited OSCC cell viabilities, migration, and invasiveness but facilitated OSCC cell apoptosis. PART1 upregulated SOCS6 through sponging miR-17-5p. Moreover, exosome-mediated lncRNA PART1 suppressed the phosphorylation of STAT3. DISCUSSION Exosome-mediated lncRNA PART1 could mediate the OSCC progression via miR-17-5p/SOCS6 axis in vitro, suggesting that lncRNA PART1 might be a target for treating OSCC.
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Affiliation(s)
- Yuheng Du
- Department of Otorhinolaryngology Head and Neck Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Yanjie Shuai
- Department of Otorhinolaryngology Head and Neck Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Hongling Wang
- Department of Otorhinolaryngology Head and Neck Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Huisheng Li
- Department of Otorhinolaryngology Head and Neck Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Yajing Li
- Department of First Surgery, Tianjin Public Security Hospital, Tianjin, China
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24
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Geng Z, Huang Y, Wu S, Zhu D, Li W. FUT8-AS1/miR-944/Fused in Sarcoma/Transcription Factor 4 Feedback Loop Participates in the Development of Oral Squamous Cell Carcinoma through Activation of Wnt/β-Catenin Signaling Pathway. THE AMERICAN JOURNAL OF PATHOLOGY 2023; 193:233-245. [PMID: 36697118 DOI: 10.1016/j.ajpath.2022.10.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Revised: 09/22/2022] [Accepted: 10/11/2022] [Indexed: 01/24/2023]
Abstract
As a common type of head and neck squamous cell carcinoma, oral squamous cell carcinoma (OSCC) is a lethal and deforming disease. Long noncoding RNAs have emerged as critical modulators in different malignancies. However, the role of fucosyltransferase 8 antisense RNA 1 (FUT8-AS1) in OSCC still remains elusive. In this study, quantitative RT-PCR and Western blot were used for the measurement of RNAs and proteins. Mechanism assays explored the putative correlation among genes. In vitro assays evaluated the changes in OSCC cell malignant phenotype, whereas in vivo assays highlighted the influence of FUT8-AS1 on tumor growth. FUT8-AS1, aberrantly up-regulated in OSCC tissues and cells, could exacerbate OSCC cell malignant behaviors. The cancerogenic property of FUT8-AS1 in OSCC was further confirmed via animal experiments. Furthermore, FUT8-AS1 enhanced the expression of transcription factor 4 (TCF4) via sponging miR-944 and recruiting fused in sarcoma (FUS), thus affecting OSCC cell biological behaviors via modulation on Wnt/β-catenin signaling activity. In addition, TCF4 was validated as the transcriptional activator of FUT8-AS1. To conclude, TCF4-mediated FUT8-AS1 could exacerbate OSCC cell malignant behaviors and facilitate tumor growth via modulation on miR-944/FUS/TCF4.
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Affiliation(s)
- Zushi Geng
- Department of Thyroid Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yinzhen Huang
- Department of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Shuang Wu
- Department of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Dandan Zhu
- Department of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Wenlu Li
- Department of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
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25
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Zheng K, Li Z, Ding X, Li H. Nutlin-3 suppresses tumorigenesis and progression of oral squamous cell carcinoma and enhances chemosensitivity to cisplatin. Cytotechnology 2023; 75:17-25. [PMID: 36713063 PMCID: PMC9880094 DOI: 10.1007/s10616-022-00556-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2021] [Accepted: 10/20/2022] [Indexed: 02/01/2023] Open
Abstract
Oral squamous cell carcinoma (OSCC) is an epithelial malignant tumor with great challenges of tumor metastasis and drug resistance. Nutlin-3 is a MDM2 inhibitor that can potently activate tumor suppressor gene p53. However, the exact role of Nutlin-3 in OSCC has not been identified yet. SCC-9 cells were treated with 0, 2.5, 5, 10, 20 μM Nutlin3. MDM2 and p53 protein levels were assessed using western blot analysis. Then, CCK8 assay, clone formation assay, TUNEL staining, wound healing and transwell assays were conducted to analyze the influences of Nutlin3 on the proliferation, apoptosis, migration, and invasion in SCC-9 cells. Moreover, SCC-9 cells were co-treated with 0, 0.5, 1, 2.5, 5 μM cisplatin and Nutlin3 to determine the effect of Nutlin3 on cisplatin chemosensitivity in OSCC. As expected, Nutlin-3 inhibited MDM2 but restored p53 in OSCC in a concentration-dependent manner. Meanwhile, Nutlin-3 suppressed the proliferation, clone formation, migration, invasion and epithelial-mesenchymal transition of SCC-9 cells and both boosted the apoptosis. In addition, Nutlin-3 caused a reduced cell viability and an elevated cell apoptosis rate in cisplatin-treated SCC-9 cells, indicating that Nutlin-3 enhanced cisplatin chemosensitivity in OSCC cells. Taken together, Nutlin-3 may suppress tumorigenesis and progression of OSCC and enhance chemosensitivity to cisplatin in OSCC.
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Affiliation(s)
- Kai Zheng
- Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Soochow University, Suzhou, 215000 Jiangsu China
| | - Zexi Li
- Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Soochow University, Suzhou, 215000 Jiangsu China
| | - Xu Ding
- Department of Oral and Maxillofacial Surgery, Jiangsu Key Laboratory of Oral Diseases, Affiliated Hospital of Stomatology, Nanjing Medical University, NO.136 Hanzhong Road, Nanjing, 210029 Jiangsu China
| | - Huaiqi Li
- Department of Oral and Maxillofacial Surgery, Jiangsu Key Laboratory of Oral Diseases, Affiliated Hospital of Stomatology, Nanjing Medical University, NO.136 Hanzhong Road, Nanjing, 210029 Jiangsu China
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26
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Therapeutic Potential of Dimethyl Fumarate in Counteract Oral Squamous Cell Carcinoma Progression by Modulating Apoptosis, Oxidative Stress and Epithelial-Mesenchymal Transition. Int J Mol Sci 2023; 24:ijms24032777. [PMID: 36769105 PMCID: PMC9917022 DOI: 10.3390/ijms24032777] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Revised: 01/17/2023] [Accepted: 01/29/2023] [Indexed: 02/05/2023] Open
Abstract
Oral squamous cell carcinoma (OSCC) is a common human tumor, that originates from buccal mucosa and the tongue, associated with a high mortality rate. Currently, the treatment for OSCC involves surgery, chemotherapy and radiotherapy; however, survival outcomes for OSCC patients remain poor. For this reason, it is necessary to investigate new therapeutic strategies to counteract the progression of OSCC. In this study, we aimed to evaluate the role of dimethyl fumarate (DMF) in modulation of OSCC progression, both in vitro and in an in vivo orthotopic xenograft model. In vitro results revealed that DMF was able to reduce the expression of anti-apoptotic factors as BCL-2 and increased the expression of pro-apoptotic factors as Bax, Caspase-3 and BID. DMF appears to be involved in the modulation of oxidative stress mediators, such as MnSOD and HO-1. Furthermore, DMF showed to reduce the migratory ability of tumor cells and to modulate the expression of markers of epithelial-mesenchymal transition (EMT), as N-cadherin and E-cadherin. The in vivo study confirmed the data obtained in vitro significantly decreasing tumor mass and also reducing oxidative stress and apoptosis. Therefore, based on these results, the use of DMF could be considered a promising strategy to counteract oral cancer progression.
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27
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Cheng T, Huang F, Zhang Y, Zhou Z. Circ_0004491 stimulates guanine nucleotide-binding protein alpha subunit to inhibit the malignant progression of oral squamous cell carcinoma by sponging miR-2278. J Dent Sci 2023; 18:237-247. [PMID: 36643221 PMCID: PMC9831788 DOI: 10.1016/j.jds.2022.05.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2022] [Revised: 05/24/2022] [Indexed: 01/18/2023] Open
Abstract
Background/purpose Circular RNA origin recognition complex subunit 4 (circORC4; ID: hsa_circ_0004491) have been confirmed to be a novel potential biomarker of oral squamous cell carcinoma (OSCC). This study aimed to explore the molecular mechanism of circ_0004491 in OSCC progression. Materials and methods Levels of circ_0004491, microRNA (miR)-2278, guanine nucleotide-binding protein alpha subunit (GNAS), Bax, Bcl-2, E-cadherin and ki-67 were detected by quantitative real-time PCR, western blotting and immunohistochemistry. The proliferation of OSCC cells was measured using colony formation assay and EdU staining. Cell apoptosis and motility were detected by flow cytometry and transwell assays respectively. Interaction between miR-2278 and circ_0004491 or GNAS was predicted by bioinformatics analysis and confirmed via luciferase reporter assay and RNA immunoprecipitation assay. Xenograft tumor model was used to analyze the role of circ_0004491 in tumor growth in vivo. Results Circ_0004491 was downregulated in OSCC tissues and cell lines. Circ_0004491 overexpression suppressed the proliferation, migration and invasion whereas facilitated the apoptosis of OSCC cells. Circ_0004491 acted as a molecular sponge for miR-2278, and circ_0004491 overexpression-mediated effect was partly reversed by miR-2278 mimic in OSCC cells. MiR-2278 interacted with the 3'UTR of GNAS. Circ_0004491 contributed to GNAS level by sponging miR-2278 in OSCC cells. GNAS knockdown restored miR-2278 inhibitor-mediated effect in OSCC cells. Circ_0004491 overexpression repressed xenograft tumor growth in vivo. Conclusion Circ_0004491 can repress OSCC progression by regulation of miR-2278/GNAS axis, providing a possible circRNA-targeted therapy for OSCC.
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Affiliation(s)
- Tao Cheng
- Department of Stomatology, Hanyang Hospital Affiliated to Medical College of Wuhan University of Science and Technology, Wuhan, China,Corresponding author. Department of StomatologyHanyang Hospital Affiliated to Medical College of Wuhan University of Science and Technology, No. 53, Ink Lake Road, Hanyang District, Wuhan, 430050, China.
| | - Feifei Huang
- Department of Respiratory Medicine, Dongxihu District People’s Hospital of Wuhan City in Hubei Province, Wuhan, China
| | - Yin Zhang
- Department of Stomatology, Hanyang Hospital Affiliated to Medical College of Wuhan University of Science and Technology, Wuhan, China
| | - Zhen Zhou
- Department of Stomatology, Hanyang Hospital Affiliated to Medical College of Wuhan University of Science and Technology, Wuhan, China
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Huang B, Wu C, Hu Y, Rao L, Yang M, Zhao M, Chen H, Li Y. Osmanthus-Loaded PVP/PVA Hydrogel Inhibits the Proliferation and Migration of Oral Squamous Cell Carcinoma Cells CAL-27. Polymers (Basel) 2022; 14:polym14245399. [PMID: 36559766 PMCID: PMC9784822 DOI: 10.3390/polym14245399] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2022] [Revised: 12/05/2022] [Accepted: 12/07/2022] [Indexed: 12/13/2022] Open
Abstract
Conventional medical agents for oral squamous cell carcinoma (OSCC) with some adverse effects no longer meet the needs of the public. In this study, the prognosis-related hub genes of osmanthus-targeted therapy for OSCC were predicted and analyzed by network pharmacology and molecular docking. Osmanthus was extracted using the ethanol reflux method and osmanthus-loaded PVP/PVA (OF/PVP/PVA) hydrogel was prepared by electron beam radiation. The molecular structure, crystal structure and microscopic morphology of hydrogels were observed by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and scanning electron microscopy (SEM), respectively. OSCC cells CAL-27 were cultured with OF/PVP/PVA hydrogel at different concentrations of extract to discover cell proliferation by MTT assay. The scratching test and JC-1 staining were used to observe the migration and mitochondrial membrane potential. Through experimental exploration, we found that a total of six prognosis-related targets were predicted, which are PYGL, AURKA, SQLE, etc., and osmanthus extract had good binding activity to AURKA. In vitro, except for proliferation inhibition, OF/PVP/PVA hydrogel prevented cell migration and changed the mitochondrial membrane potential of CAL-27 cells at a concentration equal to or greater than 50 μg/mL (p < 0.05). The addition of autophagy inhibitor chloroquine and 3-methyladenine weakened the migration inhibition of hydrogel (p < 0.05).
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Affiliation(s)
- Bin Huang
- Department of Stomatology, School of Stomatology and Ophthalmology, Xianing Medical College, Hubei University of Science and Technology, Xianning 437100, China
| | - Chizhou Wu
- Department of Stomatology, School of Stomatology and Ophthalmology, Xianing Medical College, Hubei University of Science and Technology, Xianning 437100, China
| | - Yuzhu Hu
- Department of Stomatology, School of Stomatology and Ophthalmology, Xianing Medical College, Hubei University of Science and Technology, Xianning 437100, China
| | - Lu Rao
- Hubei Key Laboratory of Radiation Chemistry and Functional Materials, Non-Power Nuclear Technology Collaborative Innovation Center, Hubei University of Science and Technology, Xianning 437100, China
| | - Mingzhe Yang
- Department of Stomatology, School of Stomatology and Ophthalmology, Xianing Medical College, Hubei University of Science and Technology, Xianning 437100, China
| | - Mengyao Zhao
- Department of Stomatology, School of Stomatology and Ophthalmology, Xianing Medical College, Hubei University of Science and Technology, Xianning 437100, China
| | - Huangqin Chen
- Department of Stomatology, School of Stomatology and Ophthalmology, Xianing Medical College, Hubei University of Science and Technology, Xianning 437100, China
- Correspondence: (H.C.); (Y.L.)
| | - Yuesheng Li
- Hubei Key Laboratory of Radiation Chemistry and Functional Materials, Non-Power Nuclear Technology Collaborative Innovation Center, Hubei University of Science and Technology, Xianning 437100, China
- Correspondence: (H.C.); (Y.L.)
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Bai J, Wu L, Wang X, Wang Y, Shang Z, Jiang E, Shao Z. Roles of Mitochondria in Oral Squamous Cell Carcinoma Therapy: Friend or Foe? Cancers (Basel) 2022; 14:cancers14235723. [PMID: 36497206 PMCID: PMC9738284 DOI: 10.3390/cancers14235723] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Revised: 11/17/2022] [Accepted: 11/20/2022] [Indexed: 11/24/2022] Open
Abstract
Oral squamous cell carcinoma (OSCC) therapy is unsatisfactory, and the prevalence of the disease is increasing. The role of mitochondria in OSCC therapy has recently attracted increasing attention, however, many mechanisms remain unclear. Therefore, we elaborate upon relative studies in this review to achieve a better therapeutic effect of OSCC treatment in the future. Interestingly, we found that mitochondria not only contribute to OSCC therapy but also promote resistance, and targeting the mitochondria of OSCC via nanoparticles is a promising way to treat OSCC.
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Affiliation(s)
- Junqiang Bai
- The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education (KLOBM), School & Hospital of Stomatology, Wuhan University, Wuhan 430089, China
| | - Luping Wu
- The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education (KLOBM), School & Hospital of Stomatology, Wuhan University, Wuhan 430089, China
| | - Xinmiao Wang
- The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education (KLOBM), School & Hospital of Stomatology, Wuhan University, Wuhan 430089, China
| | - Yifan Wang
- The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education (KLOBM), School & Hospital of Stomatology, Wuhan University, Wuhan 430089, China
| | - Zhengjun Shang
- The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education (KLOBM), School & Hospital of Stomatology, Wuhan University, Wuhan 430089, China
- Department of Oral and Maxillofacial-Head and Neck Oncology, School & Hospital of Stomatology, Wuhan University, Wuhan 430089, China
| | - Erhui Jiang
- The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education (KLOBM), School & Hospital of Stomatology, Wuhan University, Wuhan 430089, China
- Department of Oral and Maxillofacial-Head and Neck Oncology, School & Hospital of Stomatology, Wuhan University, Wuhan 430089, China
- Correspondence: (E.J.); (Z.S.); Tel.: +86-27-87686215 (E.J. & Z.S.)
| | - Zhe Shao
- The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education (KLOBM), School & Hospital of Stomatology, Wuhan University, Wuhan 430089, China
- Department of Oral and Maxillofacial-Head and Neck Oncology, School & Hospital of Stomatology, Wuhan University, Wuhan 430089, China
- Correspondence: (E.J.); (Z.S.); Tel.: +86-27-87686215 (E.J. & Z.S.)
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Yu H, Li T, Mao X. Expression and Significance of Sex-Determining Region Y (SRY)–Box 12 (SOX12) in Oral Squamous Cell Carcinoma. J BIOMATER TISS ENG 2022. [DOI: 10.1166/jbt.2022.3147] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
Oral squamous cell carcinoma (OSCC) is a ubiquitous malignancy and is associated with high mortality. Accumulating evidence indicates that transcription factors play a pivotal role in the progression of OSCC. This study was aimed to investigate the expression of SOX12 in OSCC and its
significance. SOX12 expression in OSCC tissues was analyzed through TCGA databases and then tested by Western blot and qRT-PCR analysis. Moreover, SOX12 was silenced by RNA interference in OSCC cells (SCC-25 and SCC-4), and the growth ability of OSCC cells was examined using MTT assay. The
level of SOX12 was upregulated in OSCC according to the TCGA results, which was further confirmed in the OSCC cell lines. Patients with high SOX12 expression had shorter overall survival (OS) than those with low SOX12 expression. High expression of SOX12 is positively correlated with T stage
of OSCC. In addition, MTT analysis indicated that silencing of SOX12 resulted in reduced OSCC cell proliferation. Taken together, the high expression of SOX12 in OSCC indicates that SOX12 gene may play an essential role in OSCC. Our research indicates that SOX12 expression could be a predictive
biomarker and is a potential therapeutic target for OSCC.
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Affiliation(s)
- Huijie Yu
- Department of Stomatology, The People’s Hospital of Dongying, Shandong, 257000, China
| | - Tianhua Li
- Department of Stomatology, The People’s Hospital of Dongying, Shandong, 257000, China
| | - Xuemei Mao
- Department of Stomatology, The People’s Hospital of Dongying, Shandong, 257000, China
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Feng L, Yin K, Zhang S, Chen Z, Bao Y, Li T. Anti-PD-1 Therapy is Beneficial for the Survival of Patients with Oral Squamous Cell Carcinoma. Cancer Manag Res 2022; 14:2723-2731. [PMID: 36133741 PMCID: PMC9482888 DOI: 10.2147/cmar.s368738] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Accepted: 09/07/2022] [Indexed: 11/23/2022] Open
Abstract
Background Oral squamous cell carcinoma (OSCC) is one of the most common malignant tumors of the head and neck. Programmed cell death protein 1 (PD-1), and programmed cell death 1 ligand 1 (PD-L1) are often overexpressed in OSCC patients, and their expression level is closely related to tumor prognosis. The objectives of this study were: 1) to evaluate the impact of anti-PD-1 treatment on the immune system and prognosis of OSCC patients and 2) to find possible associations between T-cell immunity and anti-PD-1 therapy. Methods A total of 120 patients (divided into two equal groups: “non-anti-PD1 therapy” and “anti-PD1 therapy”) with pathologically diagnosed OSCC participated in the study. Fresh peripheral blood samples (1 mL) were collected 2 days before and 20 days after the treatment. Heparin was used as an anticoagulant. Kaplan–Meier curves were plotted to compare the non-anti-PD-1 therapy and anti-PD-1 therapy groups. Results Based on the Spearman-rho test, we found a significant correlation between anti-PD-1 treatment and survival time (P<0.001). Univariate/multivariate Cox regression analysis revealed that anti-PD-1 therapy is a significant independent risk factor of 5-year overall survival (OS) in OSCC patients (HR: 0.110, 95% CI: 0.062–0.195, P<0.001). One-way ANOVA showed that the mean levels of IFN-γ and IL-2 and numbers of CD4+ T cells were significantly increased in the anti-PD-1 therapy group compared with the non-anti PD-1 therapy group (control). The was no change in the number of CD8+ cells between the two groups. Kaplan–Meier curve results showed that the OS of patients in the anti-PD-1 therapy group was significantly longer than that in the non-anti-PD-1 therapy group. Conclusion Anti-PD-1 therapy is beneficial to the survival and prognosis of patients with OSCC, improves T-cell immunity, and enhances tumor regression.
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Affiliation(s)
- Liang Feng
- Department of Stomatology, Baoding First Central Hospital, Baoding, Hebei, People's Republic of China
| | - Ke Yin
- Department of Stomatology, Xingtai People's Hospital, Xingtai, Hebei, People's Republic of China
| | - Suxin Zhang
- Department of Stomatology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China
| | - Zhong Chen
- Department of Stomatology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China
| | - Yang Bao
- Department of Stomatology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China
| | - Tianke Li
- Department of Stomatology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China
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Yu H, Tao S, She W, Liu M, Wu Y, Lyu J. Analysis of suicide risk in adult US patients with squamous cell carcinoma: a retrospective study based on the Surveillance, Epidemiology and End Results database. BMJ Open 2022; 12:e061913. [PMID: 36109023 PMCID: PMC9478846 DOI: 10.1136/bmjopen-2022-061913] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Accepted: 08/25/2022] [Indexed: 12/24/2022] Open
Abstract
OBJECTIVES The purpose of this study was to determine the risk factors for suicide in patients with squamous cell carcinoma (SCC) in the USA. SETTING Patients with SCC diagnosed between 1975 and 2017 from the Surveillance, Epidemiology and End Results (SEER) database were selected for this study. PARTICIPANTS This study included patients with SCC older than 20 years who were diagnosed between 1975 and 2017. PRIMARY AND SECONDARY OUTCOME MEASURES The general population included in data from the US Centers for Disease Control and Prevention were used to calculate the suicide rate and standardised mortality rate (SMR) of SCC patients. Univariate and multivariate Cox regression analyses were used to identify risk factors for suicide in patients with SCC. RESULTS There were 415 268 SCC patients registered in the SEER database, among which 1157 cases of suicide were found, comprising a total of 2 289 772 person-years. The suicide rate for patients with SCC was 50.53 per 100 000 person-years, and the SMR was 4.13 (95% CI 3.90 to 4.38). The Cox regression analyses showed that the factors related to a high risk of suicide among patients with SCC included being male (vs female: HR 5.36, 95% CI 4.51 to 6.38, p<0.001), older at the diagnosis (70-79 vs ≤39 years: HR 1.46, 95% CI 1.09 to 2.08, p=0.012; ≥80 vs ≤39 years: HR 1.48, 95% CI 1.05 to 2.08, p=0.025) and white (vs black, HR 2.97, 95% CI 2.20 to 4.02, p<0.001) and surgery (vs not performed: HR 0.65, 95% CI 0.57 to 0.74, p<0.001). CONCLUSIONS Compared with the general population, patients with SCC in the USA have a higher risk of suicide. Being male, older at the diagnosis, white and having a higher histological grade are risk factors for suicide in patients.
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Affiliation(s)
- Haohui Yu
- Jinan University First Affiliated Hospital, Guangzhou, Guangdong, China
| | - Shengru Tao
- Jinan University First Affiliated Hospital, Guangzhou, Guangdong, China
| | - Wenli She
- Jinan University First Affiliated Hospital, Guangzhou, Guangdong, China
| | - Min Liu
- Jinan University First Affiliated Hospital, Guangzhou, Guangdong, China
| | - Yayun Wu
- Jinan University First Affiliated Hospital, Guangzhou, Guangdong, China
| | - Jun Lyu
- Jinan University First Affiliated Hospital, Guangzhou, Guangdong, China
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Shao Z, Wang X, Li Y, Hu Y, Li K. The role of long noncoding RNAs as regulators of the epithelial–Mesenchymal transition process in oral squamous cell carcinoma cells. Front Mol Biosci 2022; 9:942636. [PMID: 36106022 PMCID: PMC9465078 DOI: 10.3389/fmolb.2022.942636] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2022] [Accepted: 08/01/2022] [Indexed: 11/30/2022] Open
Abstract
Oral squamous cell carcinoma (OSCC) is a highly invasive and relatively prevalent cancer, accounting for around 3% of all cancers diagnosed. OSCC is associated with bad outcomes, with only 50% overall survival (OS) after five years. The ability of OSCC to invade local and distant tissues relies on the induction of the epithelial–mesenchymal transition (EMT), wherein epithelial cells shed their polarity and cell-to-cell contacts and acquire mesenchymal characteristics. Consequently, a comprehensive understanding of how tumor cell EMT induction is regulated has the potential of direct attempts to prevent tumor progression and metastasis, resulting in better patient outcomes. Several recent studies have established the significance of particular long noncoding RNAs (lncRNAs) in the context of EMT induction. Moreover, lncRNAs regulate a vast array of oncogenic pathways. With a focus on the mechanisms by which the underlined lncRNAs shape the metastatic process and a discussion of their potential utility as clinical biomarkers or targets for therapeutic intervention in patients with OSCC, the present review thus provides an overview of the EMT-related lncRNAs that are dysregulated in OSCC.
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Affiliation(s)
- Zifei Shao
- Xiangya School of Stomatology, Central South University, Changsha, Hunan, China
| | - Xiang Wang
- Xiangya School of Stomatology, Central South University, Changsha, Hunan, China
| | - Yiyang Li
- Xiangya School of Stomatology, Central South University, Changsha, Hunan, China
| | - Yanjia Hu
- Xiangya School of Stomatology, Central South University, Changsha, Hunan, China
- Hunan Clinical Research Center of Oral Major Diseases and Oral Health and Xiangya Stomatological Hospital, Changsha, China
- *Correspondence: Yanjia Hu, ; Kun Li,
| | - Kun Li
- Xiangya School of Stomatology, Central South University, Changsha, Hunan, China
- Hunan Clinical Research Center of Oral Major Diseases and Oral Health and Xiangya Stomatological Hospital, Changsha, China
- *Correspondence: Yanjia Hu, ; Kun Li,
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Fang Z, Wang F, Zhang M, Huang H, Lin Z. Identification of Co-Expression Modules and Genes Associated With Tumor Progression in Oral Squamous Cell Carcinoma. Pathol Oncol Res 2022; 28:1610481. [PMID: 36052378 PMCID: PMC9426548 DOI: 10.3389/pore.2022.1610481] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2022] [Accepted: 06/28/2022] [Indexed: 12/24/2022]
Abstract
Oral squamous cell carcinoma (OSCC) is a common head-and-neck cancer with a deficiency of early diagnosis and poor prognosis. To identify potential diagnostic and prognostic markers of OSCC, we firstly used weighted gene co-expression network analysis (WGCNA) to build a co-expression module from GSE42743. Next, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses on specified units from selected modules utilizing Database for Annotation, Visualization, and Integrated Discovery (DAVID). Additionally, we identified and validate hub genes of these specified modules from multiple datasets like GEPIA and TCGA. In total 16 co-expression modules were built by 17,238 genes of 74 tumor samples utilizing WGCNA. Through pathway and functional enrichment analysis, the turquoise module was most firmly relevant to the cell cycle, oocyte meiosis, and p53 signaling pathway. Hub genes VRK1, NUP37, HMMR, SPC25, and RUVBL1 were identified to be related to oral cancer at both molecular level and clinical levels. The expressions of these genes differed in tumor tissues and normal tissues. Meanwhile, patients with high hub gene expression had a poor prognosis clinically. To conclude, five hub genes were identified to be relevant to oral cancer from the molecular level and the clinical level. Therefore, the detection of these genes was of great significance. They can be regarded as diagnostic and prognostic biomarkers for oral cancer. Also, they could shed light on the improvement of patients’ overall survival and prognosis, which needs further analysis in the future.
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Affiliation(s)
- Zhijie Fang
- Department of Otolaryngology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, China
| | - Feifei Wang
- Department of Nursing, Suzhou BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University, Suzhou, China
| | - Mengya Zhang
- Department of Otolaryngology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, China
| | - Hua Huang
- Department of Otolaryngology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, China
| | - Zhiqiang Lin
- Department of Otolaryngology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, China
- *Correspondence: Zhiqiang Lin,
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Lu CC, Tsai HC, Yang DY, Wang SW, Tsai MH, Hua CH, Chen KJ, Chen MYC, Lien MY, Tang CH. The Chemokine CCL4 Stimulates Angiopoietin-2 Expression and Angiogenesis via the MEK/ERK/STAT3 Pathway in Oral Squamous Cell Carcinoma. Biomedicines 2022; 10:biomedicines10071612. [PMID: 35884919 PMCID: PMC9313364 DOI: 10.3390/biomedicines10071612] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2022] [Revised: 06/24/2022] [Accepted: 07/04/2022] [Indexed: 11/16/2022] Open
Abstract
Oral squamous cell carcinoma (OSCC) is a common malignant tumor with a poor prognosis and is a major public health burden in Taiwan. Angiogenesis, the formation of new blood vessels, promotes tumor proliferation, maintenance, and metastasis. Angiopoietin 2 (Angpt2), a mitogen with a strong angiogenic effect, is highly specific to endothelial cells and a key player in angiogenesis. The inflammatory chemokine (C-C motif) ligand 4 (CCL4) is also important in the pathogenesis and progression of cancer. In this study, an analysis of records from The Cancer Genome Atlas (TCGA) database found higher CCL4 expression in oral cancer tissue than in normal healthy tissue. CCL4 treatment of oral cancer cells upregulated Angpt2 expression and stimulated mitogen-activated protein kinase kinase (MEK), extracellular signal-regulated kinase 1/2 (ERK), and signal transducer and activator of transcription 3 (STAT3) phosphorylation. Transfection of oral cancer cells with MEK, ERK, and STAT3 inhibitors and their small interfering RNAs inhibited CCL4-induced promotion of Angpt2 expression and angiogenesis. In a mouse model of OSCC, CCL4-treated cells promoted neovascularization in implanted Matrigel plugs, whereas inhibiting CCL4 expression suppressed Angpt2 expression and angiogenesis. CCL4 shows promise as a new molecular therapeutic target for inhibiting angiogenesis and metastasis in OSCC.
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Affiliation(s)
- Chien-Chi Lu
- Department of Otorhinolaryngology, China Medical University Hospital, Taichung 404327, Taiwan; (C.-C.L.); (M.-H.T.); (C.-H.H.)
| | - Hsiao-Chi Tsai
- School of Medicine, China Medical University, Taichung 404328, Taiwan;
- Division of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital, Taichung 404327, Taiwan
| | - Dong-Ying Yang
- Graduate Institute of Basic Medical Science, China Medical University, Taichung 404328, Taiwan;
| | - Shih-Wei Wang
- Institute of Biomedical Science, Mackay Medical College, New Taipei City 252005, Taiwan;
- Department of Medicine, Mackay Medical College, New Taipei City 252005, Taiwan
- School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807378, Taiwan
| | - Ming-Hsui Tsai
- Department of Otorhinolaryngology, China Medical University Hospital, Taichung 404327, Taiwan; (C.-C.L.); (M.-H.T.); (C.-H.H.)
| | - Chun-Hung Hua
- Department of Otorhinolaryngology, China Medical University Hospital, Taichung 404327, Taiwan; (C.-C.L.); (M.-H.T.); (C.-H.H.)
| | - Kwei-Jing Chen
- School of Dentistry, China Medical University, Taichung 404328, Taiwan; (K.-J.C.); (M.Y.-C.C.)
- Department of Dentistry, China Medical University Hospital, Taichung 404327, Taiwan
| | - Michael Yuan-Chien Chen
- School of Dentistry, China Medical University, Taichung 404328, Taiwan; (K.-J.C.); (M.Y.-C.C.)
- Department of Dentistry, China Medical University Hospital, Taichung 404327, Taiwan
| | - Ming-Yu Lien
- School of Medicine, China Medical University, Taichung 404328, Taiwan;
- Division of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital, Taichung 404327, Taiwan
- Correspondence: (M.-Y.L.); (C.-H.T.); Tel.: +886-2205-2121 (ext. 1513) (M.-Y.L.); +886-2205-2121 (ext. 7726) (C.-H.T.)
| | - Chih-Hsin Tang
- School of Medicine, China Medical University, Taichung 404328, Taiwan;
- Graduate Institute of Basic Medical Science, China Medical University, Taichung 404328, Taiwan;
- Graduate Institute of Biomedical Sciences, China Medical University, Taichung 404328, Taiwan
- Chinese Medicine Research Center, China Medical University, Taichung 404333, Taiwan
- Department of Biotechnology, College of Health Science, Asia University, Taichung 413305, Taiwan
- Correspondence: (M.-Y.L.); (C.-H.T.); Tel.: +886-2205-2121 (ext. 1513) (M.-Y.L.); +886-2205-2121 (ext. 7726) (C.-H.T.)
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Wang L, Ma X, Yu J, Lou Y. Negative regulation of miR-1288-3p/KRT4 axis through a circular RNA in oral cancer. J Biochem Mol Toxicol 2022; 36:e23118. [PMID: 35707935 DOI: 10.1002/jbt.23118] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Revised: 04/21/2022] [Accepted: 05/28/2022] [Indexed: 11/09/2022]
Abstract
Circular RNA (circRNA) has been widely reported to be involved in oral squamous cell carcinoma (OSCC), while the way in which hsa_circ_0096042 affects OSCC remains unclear. The hsa_circ_0096042, miR-1288-3p, and KRT4 expression in OSCC tissues and cell lines were detected by quantitative reverse-transcription polymerase chain reaction. Based on the overexpression of hsa_circ_0096042, miR-1288-3p, or KRT4, the viability and proliferation of OSCC cells were analyzed by cell counting kit-8 and colony formation assay, and the protein levels of Bax and Bcl-2 were detected by western blot, and the growth of cancer cells in vivo was analyzed by xenograft experiment. In addition, the database was used to predict the binding of hsa_circ_0096042, miR-1288-3p, and KRT4, and the interaction was confirmed by luciferase, RIP, and RNA pull-down assay. Hsa_circ_0096042 and KRT4 were abnormally downregulated and miR-1288-3p was upregulated in OSCC. Hsa_circ_0096042 overexpression restrained the proliferation and viability of OSCC cells, facilitated apoptosis, and inhibited the growth of cancer cells in vivo. Hsa_circ_0096042 bound to miR-1288-3p, whose upregulation promoted OSCC progression and eliminated the effects of overexpression of hsa_circ_0096042 on OSCC cells. KRT4 was the target gene for miR-1288-3p. Hsa_circ_0096042 plays an antitumor role in OSCC via miR-1288-3p/KRT4 axis.
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Affiliation(s)
- Lu Wang
- Department of stomatology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Henan University People's Hospital, Zhengzhou, Henan, China
| | - Xin Ma
- Department of stomatology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Henan University People's Hospital, Zhengzhou, Henan, China
| | - Jie Yu
- Department of stomatology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Henan University People's Hospital, Zhengzhou, Henan, China
| | - Ying Lou
- Department of stomatology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Henan University People's Hospital, Zhengzhou, Henan, China
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Adeoye J, Sakeen Alkandari A, Tan JY, Wang W, Zhu WY, Thomson P, Zheng LW, Choi SW, Su YX. Performance of a simplified scoring system for risk stratification in oral cancer and oral potentially malignant disorders screening. J Oral Pathol Med 2022; 51:464-473. [PMID: 35312123 DOI: 10.1111/jop.13293] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2022] [Accepted: 03/08/2022] [Indexed: 11/30/2022]
Abstract
BACKGROUND Impact and efficiency of oral cancer and oral potentially malignant disorders screening are most realized in "at-risk" individuals. However, tools that can provide essential knowledge on individuals' risks are not applied in risk-based screening. This study aims to optimize a simplified risk scoring system for risk stratification in organized oral cancer and oral potentially malignant disorders screening. METHODS Participants were invited to attend a community-based oral cancer and oral potentially malignant disorders screening program in Hong Kong. Visual oral examination was performed for all attendees and information on sociodemographic characteristics as well as habitual, lifestyle, familial, and comorbidity risk factors were obtained. Individuals' status of those found to have suspicious lesions following biopsy and histopathology were classified as positive/negative and this outcome was used in a multiple logistic regression analysis with variables collected during screening. Odds ratio weightings were then used to develop a simplified risk scoring system which was validated in an external cohort. RESULTS Of 979 participants, 4.5% had positive status following confirmatory diagnosis. A 12-variable simplified risk scoring system with weightings was generated with an AUC, sensitivity, and specificity of 0.82, 0.71, and 0.78 for delineating high-risk cases. Further optimization on the validation cohort of 491 participants yielded a sensitivity and specificity of 0.75 and 0.87 respectively. CONCLUSIONS The simplified risk scoring system was able to stratify oral cancer and oral potentially malignant disorders risk with satisfactory sensitivity and specificity and can be applied in risk-based disease screening.
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Affiliation(s)
- John Adeoye
- Division of Oral and Maxillofacial Surgery, Faculty of Dentistry, University of Hong Kong, Hong Kong, SAR, China
| | - Abdulrahman Sakeen Alkandari
- Division of Oral and Maxillofacial Surgery, Faculty of Dentistry, University of Hong Kong, Hong Kong, SAR, China
| | - Jia Yan Tan
- Division of Oral and Maxillofacial Surgery, Faculty of Dentistry, University of Hong Kong, Hong Kong, SAR, China
| | - Weilan Wang
- Division of Oral and Maxillofacial Surgery, Faculty of Dentistry, University of Hong Kong, Hong Kong, SAR, China
| | - Wang-Yong Zhu
- Division of Oral and Maxillofacial Surgery, Faculty of Dentistry, University of Hong Kong, Hong Kong, SAR, China
| | - Peter Thomson
- College of Medicine and Dentistry, James Cook University, Cairns, Queensland, Australia
| | - Li-Wu Zheng
- Division of Oral and Maxillofacial Surgery, Faculty of Dentistry, University of Hong Kong, Hong Kong, SAR, China
| | - Siu-Wai Choi
- Division of Oral and Maxillofacial Surgery, Faculty of Dentistry, University of Hong Kong, Hong Kong, SAR, China
| | - Yu-Xiong Su
- Division of Oral and Maxillofacial Surgery, Faculty of Dentistry, University of Hong Kong, Hong Kong, SAR, China
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Wang Z, Zhang T, Wu W, Wu L, Li J, Huang B, Liang Y, Li Y, Li P, Li K, Wang W, Guo R, Wang Q. Detection and Localization of Solid Tumors Utilizing the Cancer-Type-Specific Mutational Signatures. Front Bioeng Biotechnol 2022; 10:883791. [PMID: 35547159 PMCID: PMC9081532 DOI: 10.3389/fbioe.2022.883791] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2022] [Accepted: 04/07/2022] [Indexed: 11/17/2022] Open
Abstract
Accurate detection and location of tumor lesions are essential for improving the diagnosis and personalized cancer therapy. However, the diagnosis of lesions with fuzzy histology is mainly dependent on experiences and with low accuracy and efficiency. Here, we developed a logistic regression model based on mutational signatures (MS) for each cancer type to trace the tumor origin. We observed MS could distinguish cancer from inflammation and healthy individuals. By collecting extensive datasets of samples from ten tumor types in the training cohort (5,001 samples) and independent testing cohort (2,580 samples), cancer-type-specific MS patterns (CTS-MS) were identified and had a robust performance in distinguishing different types of primary and metastatic solid tumors (AUC:0.76 ∼ 0.93). Moreover, we validated our model in an Asian population and found that the AUC of our model in predicting the tumor origin of the Asian population was higher than 0.7. The metastatic tumor lesions inherited the MS pattern of the primary tumor, suggesting the capability of MS in identifying the tissue-of-origin for metastatic cancers. Furthermore, we distinguished breast cancer and prostate cancer with 90% accuracy by combining somatic mutations and CTS-MS from cfDNA, indicating that the CTS-MS could improve the accuracy of cancer-type prediction by cfDNA. In summary, our study demonstrated that MS was a novel reliable biomarker for diagnosing solid tumors and provided new insights into predicting tissue-of-origin.
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Affiliation(s)
- Ziyu Wang
- Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China
- Department of Bioinformatics, Nanjing Medical University, Nanjing, China
- Institute for Brain Tumors, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China
| | - Tingting Zhang
- Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China
- Department of Bioinformatics, Nanjing Medical University, Nanjing, China
- Institute for Brain Tumors, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China
| | - Wei Wu
- Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China
- Department of Bioinformatics, Nanjing Medical University, Nanjing, China
- Institute for Brain Tumors, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China
| | - Lingxiang Wu
- Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China
- Department of Bioinformatics, Nanjing Medical University, Nanjing, China
- Institute for Brain Tumors, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China
| | - Jie Li
- Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China
- Department of Bioinformatics, Nanjing Medical University, Nanjing, China
- Institute for Brain Tumors, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China
| | - Bin Huang
- Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China
- Department of Bioinformatics, Nanjing Medical University, Nanjing, China
- Institute for Brain Tumors, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China
| | - Yuan Liang
- Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China
- Department of Bioinformatics, Nanjing Medical University, Nanjing, China
- Institute for Brain Tumors, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China
| | - Yan Li
- Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China
- Department of Bioinformatics, Nanjing Medical University, Nanjing, China
- Institute for Brain Tumors, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China
| | - Pengping Li
- Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China
- Department of Bioinformatics, Nanjing Medical University, Nanjing, China
- Institute for Brain Tumors, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China
| | - Kening Li
- Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China
- Department of Bioinformatics, Nanjing Medical University, Nanjing, China
- Institute for Brain Tumors, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China
- *Correspondence: Kening Li, ; Wei Wang, ; Renhua Guo, ; Qianghu Wang,
| | - Wei Wang
- Department of Thoracic Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
- *Correspondence: Kening Li, ; Wei Wang, ; Renhua Guo, ; Qianghu Wang,
| | - Renhua Guo
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
- *Correspondence: Kening Li, ; Wei Wang, ; Renhua Guo, ; Qianghu Wang,
| | - Qianghu Wang
- Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China
- Department of Bioinformatics, Nanjing Medical University, Nanjing, China
- Institute for Brain Tumors, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China
- *Correspondence: Kening Li, ; Wei Wang, ; Renhua Guo, ; Qianghu Wang,
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Gu Y, Tang S, Wang Z, Cai L, Shen Y, Zhou Y. Identification of key miRNAs and targeted genes involved in the progression of oral squamous cell carcinoma. J Dent Sci 2022; 17:666-676. [PMID: 35756810 PMCID: PMC9201551 DOI: 10.1016/j.jds.2021.08.016] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2021] [Revised: 08/25/2021] [Indexed: 02/03/2023] Open
Abstract
Background/purpose Oral squamous cell carcinoma (OSCC) is one of the most common types of head and neck squamous cell carcinoma. Accurate biomarkers are needed for early diagnosis and prognosis of OSCC. MicroRNAs (miRNAs) have shown great values in different types of cancers including OSCC. However, most of the miRNAs involved in the development of OSCC remain uncovered. This study aimed to identify hub miRNAs and mRNAs in OSCC. Materials and methods We explored the roles of key miRNAs, target genes and their relationships in OSCC using an integrated bioinformatics approach. Initially, Two OSCC microarray datasets from the Gene Expression Omnibus database were obtained to analyze miRNA expression. MiRNA-targeted mRNAs were acquired, and gene ontology/kyoto encyclopedia of genes and genomes analyses were performed. Thereafter, we constructed a protein–protein interaction (PPI) network to identify hub genes and a miRNA-mRNA interaction network was used to identify key miRNAs. Furthermore, differential gene expression and Kaplan–Meier Plotter survival analysis was performed to evaluate their potential clinical application values. Results Four upregulated, two downregulated miRNAs and 608 target genes of the differentially expressed miRNAs were identified. The PPI and miRNA-mRNA interaction networks highlighted 10 hub genes and two key miRNAs, and pathway analyses showed their correlative involvement in tumorigenesis-related processes. Of these miRNAs and genes, miR-125b, β-actin, vinculin and histone deacetylase 1 were correlated with overall survival (P < 0.05). Conclusion These findings indicate that miR-21 and miR-125b, associated with the 10 hub genes, jointly participate in OSCC tumorigenesis, offering insight into the molecular mechanisms underlying OSCC as potential targets for early diagnosis, treatment and prognosis.
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Izumi A, Yamamoto K, Kawaguchi M, Yamashita F, Fukushima T, Kiwaki T, Tanaka H, Yamashita Y, Kataoka H. Insufficiency of hepatocyte growth factor activator inhibitor-1 confers lymphatic invasion of tongue carcinoma cells. Cancer Sci 2022; 113:2179-2193. [PMID: 35332604 PMCID: PMC9207362 DOI: 10.1111/cas.15346] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Revised: 03/15/2022] [Accepted: 03/19/2022] [Indexed: 11/29/2022] Open
Abstract
Hepatocyte growth factor (HGF) activator inhibitor type‐1 (HAI‐1), encoded by the SPINT1 gene, is a transmembrane protease inhibitor that regulates membrane‐anchored serine proteases, particularly matriptase. Here, we explored the role of HAI‐1 in tongue squamous cell carcinoma (TSCC) cells. An immunohistochemical study of HAI‐1 in surgically resected TSCC revealed the cell surface immunoreactivity of HAI‐1 in the main portion of the tumor. The immunoreactivity decreased in the infiltrative front, and this decrease correlated with enhanced lymphatic invasion as judged by podoplanin immunostaining. In vitro homozygous deletion of SPINT1 (HAI‐1KO) in TSCC cell lines (HSC3 and SAS) suppressed the cell growth rate but significantly enhanced invasion in vitro. The loss of HAI‐1 resulted in enhanced pericellular activities of proteases, such as matriptase and urokinase‐type plasminogen activator, which induced activation of HGF/MET signaling in the co‐culture with pro‐HGF‐expressing fibroblasts and plasminogen‐dependent plasmin generation, respectively. The enhanced plasminogen‐dependent plasmin generation was abrogated partly by matriptase silencing. Culture supernatants of HAI‐1KO cells had enhanced potency for converting the proform of vascular endothelial growth factor‐C (VEGF‐C), a lymphangiogenesis factor, into the mature form in a plasminogen‐dependent manner. Furthermore, HGF significantly stimulated VEGF‐C expression in TSCC cells. Orthotopic xenotransplantation into nude mouse tongue revealed enhanced lymphatic invasion of HAI‐1KO TSCC cells compared to control cells. Our results suggest that HAI‐1 insufficiency leads to dysregulated pericellular protease activity, which eventually orchestrates robust activation of protease‐dependent growth factors, such as HGF and VEGF‐C, in a tumor microenvironment to contribute to TSCC progression.
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Affiliation(s)
- Aya Izumi
- Section of Oncopathology and Regenerative Biology, Department of Pathology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan
| | - Koji Yamamoto
- Section of Oncopathology and Regenerative Biology, Department of Pathology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan
| | - Makiko Kawaguchi
- Section of Oncopathology and Regenerative Biology, Department of Pathology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan
| | - Fumiki Yamashita
- Section of Oncopathology and Regenerative Biology, Department of Pathology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan
| | - Tsuyoshi Fukushima
- Section of Oncopathology and Regenerative Biology, Department of Pathology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan
| | - Takumi Kiwaki
- Section of Oncopathology and Regenerative Biology, Department of Pathology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan
| | - Hiroyuki Tanaka
- Section of Oncopathology and Regenerative Biology, Department of Pathology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan
| | - Yoshihiro Yamashita
- Department of Oral and Maxillofacial Surgery, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan
| | - Hiroaki Kataoka
- Section of Oncopathology and Regenerative Biology, Department of Pathology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan
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Zhao C, Yang Y, Cui X, Shan Y, Xue J, Jiang D, Sun J, Li N, Li Z, Yang A. Self-Powered Electrical Impulse Chemotherapy for Oral Squamous Cell Carcinoma. MATERIALS (BASEL, SWITZERLAND) 2022; 15:2060. [PMID: 35329513 PMCID: PMC8954269 DOI: 10.3390/ma15062060] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/09/2022] [Revised: 02/27/2022] [Accepted: 03/06/2022] [Indexed: 01/13/2023]
Abstract
Oral squamous cell carcinoma (OSCC) is a common oral cancer of the head and neck, which causes tremendous physical and mental pain to people. Traditional chemotherapy usually results in drug resistance and side effects, affecting the therapy process. In this study, a self-powered electrical impulse chemotherapy (EIC) method based on a portable triboelectric nanogenerator (TENG) was established for OSCC therapy. A common chemotherapeutic drug, doxorubicin (DOX), was used in the experiment. The TENG designed with zigzag structure had a small size of 6 cm × 6 cm, which could controllably generate the fixed output of 200 V, 400 V and 600 V. The electrical impulses generated by the TENG increased the cell endocytosis of DOX remarkably. Besides, a simply and ingeniously designed microneedle electrode increased the intensity of electric field (EF) between two adjacent microneedle tips compared with the most used planar interdigital electrode at the same height, which was more suitable for three-dimensional (3D) cells or tissues. Based on the TENG, microneedle electrode and DOX, the self-powered EIC system demonstrated a maximal apoptotic cell ratio of 22.47% and a minimum relative 3D multicellular tumor sphere (MCTS) volume of 160% with the drug dosage of 1 μg mL-1.
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Affiliation(s)
- Chaochao Zhao
- Department of Biomedical Engineering, School of Medicine, Foshan University, Foshan 528225, China; (C.Z.); (J.S.); (N.L.)
- Beijing Key Laboratory of Micro-Nano Energy and Sensor, Beijing Institute of Nanoenergy and Nanosystems, Chinese Academy of Sciences, Beijing 101400, China; (Y.Y.); (X.C.); (Y.S.); (J.X.); (D.J.); (Z.L.)
| | - Yuan Yang
- Beijing Key Laboratory of Micro-Nano Energy and Sensor, Beijing Institute of Nanoenergy and Nanosystems, Chinese Academy of Sciences, Beijing 101400, China; (Y.Y.); (X.C.); (Y.S.); (J.X.); (D.J.); (Z.L.)
- School of Nanoscience and Technology, University of Chinese Academy of Sciences, Beijing 101400, China
| | - Xi Cui
- Beijing Key Laboratory of Micro-Nano Energy and Sensor, Beijing Institute of Nanoenergy and Nanosystems, Chinese Academy of Sciences, Beijing 101400, China; (Y.Y.); (X.C.); (Y.S.); (J.X.); (D.J.); (Z.L.)
- School of Nanoscience and Technology, University of Chinese Academy of Sciences, Beijing 101400, China
| | - Yizhu Shan
- Beijing Key Laboratory of Micro-Nano Energy and Sensor, Beijing Institute of Nanoenergy and Nanosystems, Chinese Academy of Sciences, Beijing 101400, China; (Y.Y.); (X.C.); (Y.S.); (J.X.); (D.J.); (Z.L.)
- School of Nanoscience and Technology, University of Chinese Academy of Sciences, Beijing 101400, China
| | - Jiangtao Xue
- Beijing Key Laboratory of Micro-Nano Energy and Sensor, Beijing Institute of Nanoenergy and Nanosystems, Chinese Academy of Sciences, Beijing 101400, China; (Y.Y.); (X.C.); (Y.S.); (J.X.); (D.J.); (Z.L.)
- School of Life Science, Beijing Institute of Technology, Beijing 100081, China
| | - Dongjie Jiang
- Beijing Key Laboratory of Micro-Nano Energy and Sensor, Beijing Institute of Nanoenergy and Nanosystems, Chinese Academy of Sciences, Beijing 101400, China; (Y.Y.); (X.C.); (Y.S.); (J.X.); (D.J.); (Z.L.)
- School of Nanoscience and Technology, University of Chinese Academy of Sciences, Beijing 101400, China
| | - Jinyan Sun
- Department of Biomedical Engineering, School of Medicine, Foshan University, Foshan 528225, China; (C.Z.); (J.S.); (N.L.)
| | - Na Li
- Department of Biomedical Engineering, School of Medicine, Foshan University, Foshan 528225, China; (C.Z.); (J.S.); (N.L.)
| | - Zhou Li
- Beijing Key Laboratory of Micro-Nano Energy and Sensor, Beijing Institute of Nanoenergy and Nanosystems, Chinese Academy of Sciences, Beijing 101400, China; (Y.Y.); (X.C.); (Y.S.); (J.X.); (D.J.); (Z.L.)
- School of Nanoscience and Technology, University of Chinese Academy of Sciences, Beijing 101400, China
| | - Anping Yang
- Department of Biomedical Engineering, School of Medicine, Foshan University, Foshan 528225, China; (C.Z.); (J.S.); (N.L.)
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Dos Santos Alves JM, Viana KF, Pereira AF, Lima Júnior RCP, Vale ML, Pereira KMA, Gondim DV. Oral carcinogenesis triggers a nociceptive behavior and c-Fos expression in rats' trigeminal pathway. Oral Dis 2022; 29:1531-1541. [PMID: 35244314 DOI: 10.1111/odi.14176] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2021] [Revised: 02/08/2022] [Accepted: 02/23/2022] [Indexed: 11/27/2022]
Abstract
OBJECTIVE To recognize changes that occur along the trigeminal pathway in oral cancer in order to establish an effective approach to pain control. METHODS Wistar rats were divided into control and 4-NQO-groups for 8, 12, 16, or 20 weeks. 4-NQO suspension was administered on the animals` tongues. Mechanical hyperalgesia, assessment of facial expressions and an open field test were performed. After euthanasia, the animals' tongues were removed for macro and microscopic analysis. c-Fos expression was analyzed in the trigeminal pathway structures. RESULTS 4-NQO induced time-dependent macroscopic lesions that were compatible with neoplastic tumors. Histopathological analysis confirmed oral squamous cell carcinoma in 50% of the animals on the 20th week. There was a significant nociceptive threshold reduction during the first two weeks, followed by a threshold return to the baseline levels, decreasing again from the 12th week. Facial nociceptive expression scores were observed on the 20th week, while increased grooming and exploratory activity were observed on the 8th week. Trigeminal ganglion showed an increased c-Fos immunoexpression on the 20th week and in the trigeminal subnucleus caudalis, it occurred on the 16th and 20th. The long-term carcinogenic exposure caused changes in the nociceptive behavior and c-Fos expression in the rats' trigeminal pathway.
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Affiliation(s)
- Joana Maria Dos Santos Alves
- Postgraduate Program in Dentistry, Faculty of Pharmacy, Dentistry and Nursing, Federal University of Ceará, Brazil
| | - Khalil Fernandes Viana
- Postgraduate Program in Dentistry, Faculty of Pharmacy, Dentistry and Nursing, Federal University of Ceará, Brazil
| | - Anamaria Falcão Pereira
- Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Brazil
| | - Roberto César Pereira Lima Júnior
- Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Brazil
| | - Mariana Lima Vale
- Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Brazil
| | - Karuza Maria Alves Pereira
- Postgraduate Program in Dentistry, Faculty of Pharmacy, Dentistry and Nursing, Federal University of Ceará, Brazil
| | - Delane Viana Gondim
- Postgraduate Program in Dentistry, Faculty of Pharmacy, Dentistry and Nursing, Federal University of Ceará, Brazil
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Isolation of cancer stem cells from skin squamous cell carcinoma. Methods Cell Biol 2022; 171:63-80. [DOI: 10.1016/bs.mcb.2022.06.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
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Tai Y, Li Y, Zhang M. Silencing of circ_OSBPL10 affects the functional behaviors of oral squamous cell carcinoma cells by the miR-299-3p/CDK6 axis. Arch Oral Biol 2022; 136:105363. [DOI: 10.1016/j.archoralbio.2022.105363] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2021] [Revised: 01/24/2022] [Accepted: 01/26/2022] [Indexed: 11/29/2022]
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Santilli M, D’Addazio G, Rexhepi I, Sinjari B, Filippini A. Multiple Free Flap Reconstruction of a Complex Intraoral Defect after Squamous Cell Carcinoma Excision: A Case Report. Medicina (B Aires) 2021; 58:medicina58010054. [PMID: 35056362 PMCID: PMC8781932 DOI: 10.3390/medicina58010054] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2021] [Revised: 12/27/2021] [Accepted: 12/28/2021] [Indexed: 11/16/2022] Open
Abstract
Background: Squamous cell carcinoma is the most frequent malignant cancer of the oral cavity. Metastasis involvement is one of the most relevant prognostic factors in terms of survival probability. Patients with oral cancers often undergo extensive en bloc resective surgery of the mandible and maxilla, with or without cervical nodal dissection, based on the presence or occult risk of regional metastases. Several factors affect the choice of flap, to recover aesthetics and function. Case Presentation: The case of a 60-year-old man who underwent maxillectomy with neck dissection as well as a reconstruction with a combination of multiple vascularized free flaps is presented. Conclusions: The excellent integration of the free flaps and the total absence of complications led to a high-quality aesthetic and functional performance of the reconstruction obtained through two different flaps. More specifically, the fibular free flap for bone reconstruction allows a two-team approach and maintains an excellent vascularization, even in case of several osteotomies for the maxillary reconstruction as reported. In addition, the use of free radial forearm flap for soft tissue reconstruction permits to obtain long caliber vessels, thus facilitating surgery without repositioning of the patient during surgery and therefore, consequently reducing surgery times.
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Affiliation(s)
- Manlio Santilli
- Department of Innovative Technologies in Medicine and Dentistry, University “G. d’Annunzio” Chieti-Pescara, 66100 Chieti, Italy; (M.S.); (G.D.); (I.R.)
- Electron Microscopy Laboratory, University “G. d’Annunzio” Chieti-Pescara, 66100 Chieti, Italy
| | - Gianmaria D’Addazio
- Department of Innovative Technologies in Medicine and Dentistry, University “G. d’Annunzio” Chieti-Pescara, 66100 Chieti, Italy; (M.S.); (G.D.); (I.R.)
- Electron Microscopy Laboratory, University “G. d’Annunzio” Chieti-Pescara, 66100 Chieti, Italy
| | - Imena Rexhepi
- Department of Innovative Technologies in Medicine and Dentistry, University “G. d’Annunzio” Chieti-Pescara, 66100 Chieti, Italy; (M.S.); (G.D.); (I.R.)
- Electron Microscopy Laboratory, University “G. d’Annunzio” Chieti-Pescara, 66100 Chieti, Italy
| | - Bruna Sinjari
- Department of Innovative Technologies in Medicine and Dentistry, University “G. d’Annunzio” Chieti-Pescara, 66100 Chieti, Italy; (M.S.); (G.D.); (I.R.)
- Electron Microscopy Laboratory, University “G. d’Annunzio” Chieti-Pescara, 66100 Chieti, Italy
- Correspondence: ; Tel.: +39-392-27471479; Fax: +39-0871-3554070
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Osan C, Chira S, Nutu AM, Braicu C, Baciut M, Korban SS, Berindan-Neagoe I. The Connection between MicroRNAs and Oral Cancer Pathogenesis: Emerging Biomarkers in Oral Cancer Management. Genes (Basel) 2021; 12:genes12121989. [PMID: 34946938 PMCID: PMC8700798 DOI: 10.3390/genes12121989] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Revised: 12/09/2021] [Accepted: 12/13/2021] [Indexed: 02/06/2023] Open
Abstract
Oral cancer is a common human malignancy that still maintains an elevated mortality rate despite scientific progress. Tumorigenesis is driven by altered gene expression patterns of proto-oncogenes and tumor-suppressor genes. MicroRNAs, a class of short non-coding RNAs involved in gene regulation, seem to play important roles in oral cancer development, progression, and tumor microenvironment modulation. As properties of microRNAs render them stable in diverse liquid biopsies, together with their differential expression signature in cancer cells, these features place microRNAs at the top of promising biomarkers for diagnostic and prognostic values. In this review, we highlight eight expression levels and functions of the most relevant microRNAs involved in oral cancer development, progression, and microenvironment sustainability. Furthermore, we emphasize the potential of using these small RNA species as non-invasive biomarkers for the early detection of oral cancerous lesions. Conclusively, we highlight the perspectives and limitations of microRNAs as novel diagnostic tools, as well as therapeutic models.
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Affiliation(s)
- Ciprian Osan
- Research Center for Functional Genomics, Biomedicine and Translational Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania; (C.O.); (S.C.); (A.M.N.); (C.B.)
| | - Sergiu Chira
- Research Center for Functional Genomics, Biomedicine and Translational Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania; (C.O.); (S.C.); (A.M.N.); (C.B.)
| | - Andreea Mihaela Nutu
- Research Center for Functional Genomics, Biomedicine and Translational Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania; (C.O.); (S.C.); (A.M.N.); (C.B.)
| | - Cornelia Braicu
- Research Center for Functional Genomics, Biomedicine and Translational Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania; (C.O.); (S.C.); (A.M.N.); (C.B.)
| | - Mihaela Baciut
- Department of Maxillofacial Surgery and Implantology, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400033 Cluj-Napoca, Romania;
| | - Schuyler S. Korban
- Department of Natural Resources & Environmental Sciences, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA;
| | - Ioana Berindan-Neagoe
- Research Center for Functional Genomics, Biomedicine and Translational Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania; (C.O.); (S.C.); (A.M.N.); (C.B.)
- Correspondence:
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Jácome-Santos H, da Silva E Silva N, Resende RG, Costa Pinheiro HH, Almeida Machado LF, de Souza Silva G, de Oliveira Costa F, Brasil-Costa I, Amoras-Alves ACB, Mesquita RA, de Melo Alves-Junior S. Simultaneous occurrence of Epstein-Barr virus (EBV) in periodontal pockets and in oral squamous cell carcinoma: a cross-sectional study. Clin Oral Investig 2021; 26:2807-2815. [PMID: 34783915 DOI: 10.1007/s00784-021-04258-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2021] [Accepted: 10/23/2021] [Indexed: 11/26/2022]
Abstract
OBJECTIVES This study aimed to investigate the detection of Epstein-Barr virus (EBV) in oral squamous cell carcinoma (OSCC) and to verify the concordance of EBV-DNA frequency in subgingival sites and in the OSCC. METHODS A cross-sectional study with 30 OSCC patients, aged from 44 to 88 years old, was conducted. Samples were collected in subgingival sites and at the OSCC, then submitted to DNA isolation, qPCR, and genotyping. Descriptive statistic was performed to report the frequency of EBV-DNA in all samples, and McNemar test was applied to verify the concordance among the EBV-DNA frequency in both sites. RESULTS The individuals presented 62 years old in average, and the majority were male (66.6%). EBV-DNA was detected in 56.7% OSCC lesions. Among the subgroup of 19 dentate individuals, high concordance (73.7%) in both EBV-DNA detection and the absence in subgingival sites and OSCC was observed, and it was statistically significant (p < 0.05). CONCLUSIONS We report the notable occurrence of EBV-DNA in OSCC; also, the presence of EBV in periodontal sites may contribute to find it in OSCC, although the possible contribution of EBV in the OSCC remains to be investigated. CLINICAL RELEVANCE The identification of this easily accessible site of EBV latent infection may help to improve the patient's quality of life by maintenance of oral/periodontal health condition and preventing further possible disorders related to the virus, and also encourages new approaches for investigating EBV, periodontitis, and OSCC.
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Affiliation(s)
- Humberto Jácome-Santos
- Laboratory of Pathology and Immunohistochemistry (LAPI), School of Dentistry, Universidade Federal do Pará (UFPA), Belém, PA, Brazil.
- Department of Oral Surgery and Pathology, School of Dentistry, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG, Brazil.
| | - Naira da Silva E Silva
- Department of Virology, Laboratory of Epstein-Barr Virus, Instituto Evandro Chagas (IEC), Belém, PA, Brazil
| | - Renata Gonçalves Resende
- Department of Stomatology & Oral and Maxillofacial Surgery, Hospital Metropolitano Odilon Behrens (HMOB), Belo Horizonte, MG, Brazil
| | - Helder Henrique Costa Pinheiro
- Laboratory of Pathology and Immunohistochemistry (LAPI), School of Dentistry, Universidade Federal do Pará (UFPA), Belém, PA, Brazil
| | | | - Guilherme de Souza Silva
- Hospital das Clínicas (HC), Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG, Brazil
| | - Fernando de Oliveira Costa
- Department of Oral Surgery and Pathology, School of Dentistry, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG, Brazil
| | - Igor Brasil-Costa
- Laboratory of Virology, Universidade Federal do Pará (UFPA), Belém, PA, Brazil
| | - Ana Cláudia Braga Amoras-Alves
- Laboratory of Pathology and Immunohistochemistry (LAPI), School of Dentistry, Universidade Federal do Pará (UFPA), Belém, PA, Brazil
| | - Ricardo Alves Mesquita
- Department of Oral Surgery and Pathology, School of Dentistry, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG, Brazil
| | - Sérgio de Melo Alves-Junior
- Laboratory of Pathology and Immunohistochemistry (LAPI), School of Dentistry, Universidade Federal do Pará (UFPA), Belém, PA, Brazil
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Zhou X, Xue D, Qiu J. Identification of biomarkers related to glycolysis with weighted gene co-expression network analysis in oral squamous cell carcinoma. Head Neck 2021; 44:89-103. [PMID: 34713497 DOI: 10.1002/hed.26910] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2020] [Revised: 09/10/2021] [Accepted: 10/05/2021] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Oral squamous cell carcinoma (OSCC) is the most common tumor in the oral cavity and maxillofacial region. Increasing evidence suggests that aerobic glycolysis plays an important role in the occurrence, development, and prognosis of OSCC. Therefore, the identification of biomarkers related to glycolysis in OSCC represents considerable potential for improving its treatment. METHODS In the present study, a single-sample gene-set enrichment analysis (ssGSEA) algorithm with weighted gene co-expression network analysis (WGCNA) were used to quantify the degree of glycolysis and identify key modules with the greatest correlation with glycolysis. RESULTS Glycolytic scores significantly correlated with prognosis. In the key module 5 HUB genes were finally selected, which displayed a robust predictive effect. The expressions of key genes were associated with glycolysis. CONCLUSIONS The research comprehensively analyzed the glycolysis of OSCC and identified several biomarkers related to glycolysis. These biomarkers may represent potential therapeutic targets for future OSCC therapy.
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Affiliation(s)
- Xiongming Zhou
- Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Danfeng Xue
- Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Jiaxuan Qiu
- Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
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Zhao Y, Yao R. Long non-coding RNA HOXA-AS3 promotes cell proliferation of oral squamous cell carcinoma through sponging microRNA miR-218-5p. Bioengineered 2021; 12:8724-8737. [PMID: 34698001 PMCID: PMC8806885 DOI: 10.1080/21655979.2021.1978196] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Increasing evidence demonstrated long non-coding RNAs (lncRNAs) play important roles in the occurrence and development of oral squamous cell carcinoma (OSCC). This study aimed to explore the role and molecular mechanism of lncRNA HOXA-AS3 in the progression of OSCC. Here, we found that the expression of lncRNA HOXA-AS3 was upregulated in OSCC tissues and cell lines compared with the para-cancerous tissues and normal human oral keratinocyte (NHOK), respectively. Inhibition of HOXA-AS3 significantly inhibited the proliferation and colony formation of OSCC cells. Further, the luciferase reporter assay showed that HOXA-AS3 was directly bound to miR-218-5p. Moreover, the expression of miR-218-5p was negatively regulated by HOXA-AS3, and miR-218-5p could inhibit the expression of collagen type I alpha1 (COL1A1) and lysophosphatidylcholine acyltransferase 1 (LPCAT1). In addition, silencing miR-218-5p reversed the inhibitory effect of HOXA-AS3 knockdown on the proliferative potential of OSCC cells. In summary, our study illustrated that HOXA-AS3 promoted cancer cell proliferation in OSCC, possibly by sponging miR-218-5p for the first time, which provides a new target or a potential diagnostic biomarker for OSCC.
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Affiliation(s)
- Yue Zhao
- Department of Pediatric Stomatology, Tianjin Stomatological Hospital, Tianjin, China
| | - Rui Yao
- Department of Pediatric Stomatology, Tianjin Stomatological Hospital, Tianjin, China
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Huanglianjiedu Decoction as an effective treatment for oral squamous cell carcinoma based on network pharmacology and experimental validation. Cancer Cell Int 2021; 21:553. [PMID: 34674717 PMCID: PMC8529748 DOI: 10.1186/s12935-021-02201-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2021] [Accepted: 09/06/2021] [Indexed: 12/03/2022] Open
Abstract
Background Oral squamous cell carcinoma (OSCC) is one of malignant tumors in oral and maxillofacial region with high fatality. Huanglianjiedu Decoction (HLJDD) is a well-known traditional Chinese medicinal prescription, which consists of Coptis chinensis Franch, Scutellaria baicalensis Georgi, Phellodendron amurense Rupr and Gardenia jasminoides J.Ellis. Some clinical studies showed HLJDD had good effectiveness on OSCC, but the mechanism is unclear. Methods In this study, potential components of HLJDD and putative targets were screened by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Combining with potential targets of OSCC searched from Therapeutic Target Database (TTD) and Online Mendelian Inheritance in Man (OMIM), we drew protein–protein interaction (PPI) network by Cytoscape v3.2.0 software. After topological analysis we got core targets and further did Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Then we did the in vitro experiments to verify the major biological processes (cell cycle, apoptosis and proliferation) and signaling pathways (mitogen-activated protein kinase (MAPK), nuclear factor-kappa B (NF-κB), protein kinase B (AKT)) on OSCC cell lines, SCC-25 and CAL-27. Results The potential component targets number of Coptis chinensis Franch, Scutellaria baicalensis Georgi, Phellodendron amurense Rupr and Gardenia jasminoides J.Ellis were 39, 93, 81and 88, respectively. Then we got 52 core targets which enriched in cell cycle, apoptosis, proliferation, MAPK activation etc. and obtained TOP30 pathways. On SCC-25 and CAL-27, HLJDD suppressed cell proliferation, induced late apoptosis and inhibited cell invasion and migration which were consistent with the results from network pharmacology analysis. Additionally, in cell cycle, we confirmed HLJDD inhibited G1 phase and arrested in S phase to reduce cell proliferation on SCC-25. In signaling pathways, HLJDD inhibited the phosphorylation of extracellular regulatory protein kinase 1/2 (ERK1/2) and NF-κB p65 (S468) on SCC-25 and CAL-27. Conclusions HLJDD played a potential therapeutic role on OSCC via inhibiting p-ERK1/2 and p-NF-κB p65 (S468). Graphical abstract ![]()
Supplementary Information The online version contains supplementary material available at 10.1186/s12935-021-02201-6.
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