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Chuang YT, Yen CY, Tang JY, Chang FR, Tsai YH, Wu KC, Chien TM, Chang HW. The modulation of immune cell death in connection to microRNAs and natural products. Front Immunol 2024; 15:1425602. [PMID: 39759512 PMCID: PMC11695430 DOI: 10.3389/fimmu.2024.1425602] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Accepted: 11/27/2024] [Indexed: 01/07/2025] Open
Abstract
Immunogenic cell death (ICD) spatiotemporally regulates damage-associated molecular patterns (DAMPs) derived from dying cancer cells to signal the immune response. Intriguingly, these DAMPs and cytokines also induce cellular responses in non-immune cells, particularly cancer cells. Several ICD-modulating natural products and miRNAs have been reported to regulate the DAMP, cytokine, and cell death responses, but they lack systemic organization and connection. This review summarizes the impacts of natural products and miRNAs on the DAMP and cytokine responses and cancer cell death responses (apoptosis, autophagy, ferroptosis, necroptosis, and pyroptosis). We establish the rationale that ICD inducers of natural products have modulating effects on miRNAs, targeting DAMPs and cytokines for immune and cancer cell death responses. In conclusion, DAMP, cytokine, and cell death responses are intricately linked in cancer cells, and they are influenced by ICD-modulating natural products and miRNAs.
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Affiliation(s)
- Ya-Ting Chuang
- Department of Biomedical Science and Environmental Biology, PhD Program in Life Sciences, College of Life Science, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ching-Yu Yen
- School of Dentistry, Taipei Medical University, Taipei, Taiwan
- Department of Oral and Maxillofacial Surgery, Chi-Mei Medical Center, Tainan, Taiwan
| | - Jen-Yang Tang
- School of Post-Baccalaureate Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Radiation Oncology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Fang-Rong Chang
- Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Yi-Hong Tsai
- Department of Pharmacy and Master Program, College of Pharmacy and Health Care, Tajen University, Pingtung, Taiwan
| | - Kuo-Chuan Wu
- Department of Computer Science and Information Engineering, National Pingtung University, Pingtung, Taiwan
| | - Tsu-Ming Chien
- School of Post-Baccalaureate Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Department of Urology, Kaohsiung Gangshan Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Hsueh-Wei Chang
- Department of Biomedical Science and Environmental Biology, PhD Program in Life Sciences, College of Life Science, Kaohsiung Medical University, Kaohsiung, Taiwan
- Center for Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
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Jiang YK, Li W, Qiu YY, Yue M. Advances in targeted therapy for human epidermal growth factor receptor 2 positive in advanced gastric cancer. World J Gastrointest Oncol 2024; 16:2318-2334. [PMID: 38994153 PMCID: PMC11236256 DOI: 10.4251/wjgo.v16.i6.2318] [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: 12/11/2023] [Revised: 04/04/2024] [Accepted: 04/18/2024] [Indexed: 06/13/2024] Open
Abstract
Emerging therapeutic methods represented by targeted therapy are effective supplements to traditional first-line chemoradiotherapy resistance. Human epidermal growth factor receptor 2 (HER2) is one of the most important targets in targeted therapy for gastric cancer. Trastuzumab combined with chemotherapy has been used as the first-line treatment for advanced gastric cancer. The safety and efficacy of pertuzumab and margetuximab in the treatment of gastric cancer have been verified. However, monoclonal antibodies, due to their large molecular weight, inability to penetrate the blood-brain barrier, and drug resistance, lead to decreased therapeutic efficacy, so it is necessary to explore the efficacy of other HER2-targeting therapies in gastric cancer. Small-molecule tyrosine kinase inhibitors, such as lapatinib and pyrrotinib, have the advantages of small molecular weight, penetrating the blood-brain barrier and high oral bioavailability, and are expected to become the drugs of choice for perioperative treatment and neoadjuvant therapy of gastric cancer after validation by large-scale clinical trials in the future. Antibo-drug conjugate, such as T-DM1 and T-DXd, can overcome the resistance of monoclonal antibodies despite their different mechanisms of tumor killing, and are a supplement for the treatment of patients who have failed the treatment of monoclonal antibodies such as trastuzumab. Therefore, after more detailed stratification of gastric cancer patients, various gastric cancer drugs targeting HER2 are expected to play a more significant role.
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Affiliation(s)
- Ya-Kun Jiang
- Department of Gastroenterology, Central Hospital Affiliated to Shandong First Medical University, Jinan 250013, Shandong Province, China
| | - Wei Li
- Health Management Center, Central Hospital Affiliated to Shandong First Medical University, Jinan 250013, Shandong Province, China
| | - Ying-Yang Qiu
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119077, Singapore
| | - Meng Yue
- Department of Gastroenterology, Central Hospital Affiliated to Shandong First Medical University, Jinan 250013, Shandong Province, China
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Heidarzadehpilehrood R, Pirhoushiaran M. Biomarker potential of competing endogenous RNA networks in Polycystic Ovary Syndrome (PCOS). Noncoding RNA Res 2024; 9:624-640. [PMID: 38571815 PMCID: PMC10988127 DOI: 10.1016/j.ncrna.2024.01.002] [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: 10/22/2023] [Revised: 12/21/2023] [Accepted: 01/08/2024] [Indexed: 04/05/2024] Open
Abstract
Polycystic ovary syndrome (PCOS) is the most common condition affecting women of reproductive age globally. PCOS continues to be the largest contributing factor to female infertility despite significant progress in our knowledge of the molecular underpinnings and treatment of the condition. The fact that PCOS is a very diverse condition makes it one of the key reasons why we haven't been able to overcome it. Non-coding RNAs (ncRNAs) are implicated in the development of PCOS, according to growing evidence. However, it is unclear how the complex regulatory relationships between the many ncRNA types contribute to the growth of this malignancy. Competing endogenous RNA (ceRNA), a recently identified mechanism in the RNA world, suggests regulatory interactions between various RNAs, including long non-coding RNAs (lncRNAs), microRNAs (miRNAs), transcribed pseudogenes, and circular RNAs (circRNAs). Recent studies on PCOS have shown that dysregulation of multiple ceRNA networks (ceRNETs) between these ncRNAs plays crucial roles in developing the defining characteristics of PCOS development. And it is believed that such a finding may open a new door for a deeper comprehension of PCOS's unexplored facets. In addition, it may be able to provide fresh biomarkers and effective therapy targets for PCOS. This review will go over the body of information that exists about the primary roles of ceRNETs before highlighting the developing involvement of several newly found ceRNETs in a number of PCOS characteristics.
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Affiliation(s)
- Roozbeh Heidarzadehpilehrood
- Department of Obstetrics & Gynaecology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400, Serdang, Selangor, Malaysia
| | - Maryam Pirhoushiaran
- Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, 1417613151, Iran
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Yang B, Wang Y, Liu T, Zhang M, Luo T. The necroptosis-related signature and tumor microenvironment immune characteristics associated with clinical prognosis and drug sensitivity analysis in stomach adenocarcinoma. Aging (Albany NY) 2024; 16:6098-6117. [PMID: 38546403 PMCID: PMC11042952 DOI: 10.18632/aging.205690] [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: 08/15/2023] [Accepted: 01/30/2024] [Indexed: 04/23/2024]
Abstract
PURPOSE Necroptosis plays an important role in the tumorigenesis, development, metastasis, and drug resistance of malignant tumors. This study explored the new model for assessing stomach adenocarcinoma (STAD) prognosis and immunotherapy by combining long noncoding RNAs associated with necroptosis. METHODS Patient clinical data and STAD gene expression profiles were curated from The Cancer Genome Atlas (TCGA). Immune-related genes were sourced from a specialized molecular database. Perl software and R software were used for data processing and analysis. Necroptosis-related lncRNAs in STAD were pinpointed via R's correlation algorithms. These lncRNAs, in conjunction with clinical data, informed the construction of a prognostic lncRNA-associated risk score model using univariate and multivariate Cox regression analyses. The model's prognostic capacity was evaluated by Kaplan-Meier survival curves and validated as an independent prognostic variable. Further, a nomogram incorporating this model with clinical parameters was developed, offering refined individual survival predictions. Subsequent analyses of immune infiltration and chemosensitivity within necroptosis-related lncRNA clusters utilized an arsenal of bioinformatic tools, culminating in RT-PCR validation of lncRNA expression. RESULTS Through rigorous Cox regression, 21 lncRNAs were implicated in the risk score model. Stratification by median risk scores delineated patients into high- and low-risk cohorts, with the latter demonstrating superior prognostic outcomes. The risk model was corroborated as an independent prognostic indicator for STAD. The integrative nomogram displayed high concordance between predicted and observed survival rates, as evidenced by calibration curves. Differential immune infiltration in risk-defined groups was illuminated by the single sample GSEA (ssGSEA), indicating pronounced immune presence in higher-risk patients. Tumor microenvironment (TME) analysis showed that cluster-C3 had the highest score in the analysis of the three TMEs. Through the differential analysis of immune checkpoints, it was found that almost all immune checkpoint-related genes were expressed differently in various tumor clusters. Among them, CD44 expression was the highest. By comparing all drug sensitivities, we screened out 29 drugs with differences in drug sensitivity across different clusters. Risk score gene expression identification results showed that these lncRNAs were abnormally expressed in gastric cancer cell lines. CONCLUSIONS This investigation provides a robust methodological advance in prognosticating and personalizing immunotherapy for STAD, leveraging quantitatively derived tumor cluster risk scores. It posits the use of necroptosis-related lncRNAs as pivotal molecular beacons for guiding therapeutic strategies and enhancing clinical outcomes in STAD.
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Affiliation(s)
- Biao Yang
- Department of General Surgery, Changhai Hospital, Naval Medical University, Shanghai 200433, China
| | - Yingnan Wang
- Henan University of Science and Technology, Henan 471000, China
| | - Tao Liu
- Department of Emergency, Changhai Hospital, Naval Medical University, Shanghai 200433, China
| | - Meijing Zhang
- Department of Oncology, Changhai Hospital, Naval Medical University, Shanghai 200433, China
| | - Tianhang Luo
- Department of General Surgery, Changhai Hospital, Naval Medical University, Shanghai 200433, China
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Chang X, Li H, Huang Z, Song C, Zhang Z, Pan W. Matrine suppresses hepatocellular carcinoma tumorigenesis by modulating circ_0055976/miR-1179/lactate dehydrogenase A axis. ENVIRONMENTAL TOXICOLOGY 2024; 39:1481-1493. [PMID: 37994612 DOI: 10.1002/tox.24041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/21/2023] [Revised: 10/13/2023] [Accepted: 11/05/2023] [Indexed: 11/24/2023]
Abstract
BACKGROUND Matrine has been identified to have anticancer activity in hepatocellular carcinoma (HCC). Circ_0055976 was highly expressed in HCC. Here, we investigated the function and relationship of Matrine and circ_0055976 in HCC tumorigenesis. METHODS Cell proliferation and invasion were detected using Cell Counting Kit-8, 5-Ethynyl-2'-deoxyuridine (EdU), colony formation and transwell assays, respectively. Cell aerobic glycolysis was evaluated by detecting glucose consumption, lactate production, and the ratios of ATP/ADP. Levels of genes and proteins were detected by quantitative real-time polymerase chain reaction and Western blotting. The target relationship between miR-1179 and circ_0055976 or lactate dehydrogenase A (LDHA) was analyzed by dual-luciferase reporter assay. The mouse xenograft model was established to conduct the in vivo assay. RESULTS Matrine suppressed HCC cell proliferation, invasion and anaerobic glycolysis in vitro. Circ_0055976 was highly expressed in HCC tissues and cells, and was reduced by Matrine treatment. Moreover, overexpression of circ_0055976 reversed the anticancer effects of Matrine in HCC cells. Mechanistically, circ_0055976/miR-1179/LDHA formed an axis. Circ_0055976 knockdown or miR-1179 overexpression impaired HCC cell proliferation, invasion, and anaerobic glycolysis, which were reversed by miR-1179 inhibition or LDHA overexpression. Meanwhile, forced expression of LDHA abolished the regulatory effects of Matrine on HCC cells. In the clinic, Matrine impeded HCC tumor growth in vivo, and this effect was boosted after circ_0055976 silencing. CONCLUSION Matrine suppressed HCC cell proliferation, invasion, and anaerobic glycolysis via circ_0055976/miR-1179/LDHA axis, providing a new insight into the clinical application of Matrine in HCC treatment.
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Affiliation(s)
- Xinfeng Chang
- Department of human anatomy, Jiangsu Vocational College of Medicine, Yancheng, China
| | - Hongwei Li
- Department of human anatomy, Gannan Medical University, Ganzhou, China
| | - Zhengchun Huang
- Department of human anatomy, Gannan Medical University, Ganzhou, China
| | - Chunhua Song
- Department of surgery, Jiangsu Vocational College of Medicine, Yancheng, China
| | - Zhihua Zhang
- Graduate Department, Gannan Medical University, Ganzhou, China
| | - Wen Pan
- Department of Physiology, Jiangsu Vocational College of Medicine, Yancheng, China
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Heydarnia E, Dorostgou Z, Hedayati N, Mousavi V, Yahyazadeh S, Alimohammadi M, Gheibi M, Heidari P, Igder S, Mafi A, Vakili O. Circular RNAs and cervical cancer: friends or foes? A landscape on circRNA-mediated regulation of key signaling pathways involved in the onset and progression of HPV-related cervical neoplasms. Cell Commun Signal 2024; 22:107. [PMID: 38341592 PMCID: PMC10859032 DOI: 10.1186/s12964-024-01494-0] [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: 09/30/2023] [Accepted: 01/20/2024] [Indexed: 02/12/2024] Open
Abstract
Cervical cancer (CC) is a common gynecologic malignancy, accounting for a significant proportion of women death worldwide. Human papillomavirus (HPV) infection is one of the major etiological causes leading to CC onset; however, genetic, and epigenetic factors are also responsible for disease expansion. Circular RNAs (circRNAs), which are known as a particular subset of non-coding RNA (ncRNA) superfamily, with covalently closed loop structures, have been reported to be involved in the progression of diverse diseases, especially neoplasms. In this framework, abnormally expressed circRNAs are in strong correlation with CC pathogenesis through regulating substantial signaling pathways. Also, these RNA molecules can be considered as promising biomarkers and therapeutic targets for CC diagnosis/prognosis and treatment, respectively. Herein, we first review key molecular mechanisms, including Wnt/β-catenin, MAPK, and PI3K/Akt/mTOR signaling pathways, as well as angiogenesis and metastasis, by which circRNAs interfere with CC development. Then, diagnostic, prognostic, and therapeutic potentials of these ncRNA molecules will be highlighted in depth.
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Affiliation(s)
- Emad Heydarnia
- Department of Medical Nanotechnology, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Zahra Dorostgou
- Department of Biochemistry, Neyshabur Branch, Islamic Azad University, Neyshabur, Iran
| | - Neda Hedayati
- School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Vahide Mousavi
- School of Medicine, Bushehr University of Medical Sciences, Bushehr, Iran
| | - Sheida Yahyazadeh
- Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mina Alimohammadi
- Student Research Committee, Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Mobina Gheibi
- Student Research Committee, Mazandaran University of Medical Sciences, Sari, Iran
| | - Parasta Heidari
- School of Medicine, Bushehr University of Medical Sciences, Bushehr, Iran.
| | - Somayeh Igder
- Department of Clinical Biochemistry, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Alireza Mafi
- Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.
- Nutrition and Food Security Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
| | - Omid Vakili
- Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.
- Autophagy Research Center, Department of Clinical Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
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Ma J, Da M. High-Mobility Group Box 1 Overexpression Predicts a Poor Prognosis and Promotes Epithelial-Mesenchymal Transition in Gastric Cancer by Activating TLR4/NF-κB Signaling. Oncology 2023; 101:786-798. [PMID: 37666221 DOI: 10.1159/000533927] [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: 07/26/2023] [Accepted: 08/29/2023] [Indexed: 09/06/2023]
Abstract
INTRODUCTION The molecular mechanism of high-mobility group box 1 (HMGB1) promoting the epithelial-mesenchymal transition (EMT) of gastric cancer (GC) has not been known well. This study aimed to explore the clinical effects of HMGB1 expression levels on the clinicopathological characteristics of patients with GC and to uncover the potential molecular mechanism which promotes tumor progression. METHODS The expression levels of HMGB1 in 125 patients with GC were detected by immunohistochemistry and Western blotting. Univariate and multivariate analyses were performed to evaluate the relationship between HMGB1 expression and clinical characteristics of patients with GC. Stable overexpression (over-HMGB1) and knockdown (sh-HMGB1) GC cell lines (AGS and MKN-45) were used to determine the effects of HMGB1 on the activation of TLR4/NF-κB signaling. Differences were considered statistically significant at p < 0.05 in two sides. RESULTS HMGB1 is highly expressed in GC tissues and cell lines. High HMGB1 expression (HR = 1.89, 95% CI: 1.44-2.39, p = 0.001) was an independent risk factor for overall survival in patients with GC. Downregulation of HMGB1 resulted in downregulation of TLR4 and NF-κB subunit (p-p65 and p-IκBα) expression, whereas the upregulated expression of HMGB1 led to increased expression of TLR4 and NF-κB subunits. Overexpression of HMGB1 promotes the upregulation of EMT-TF expression, which enhances the proliferation and migration abilities of GC cell lines. CONCLUSION HMGB1 is highly expressed in GC tissues and is associated with a poorer prognosis in patients with GC. HMGB1 activates the TLR4/NF-κB signaling pathway to promote EMT progression in GC cell lines. HMGB1 may be a critical molecule in prognosis prediction and a therapeutic target for patients with GC.
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Affiliation(s)
- Jichun Ma
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, China,
| | - Mingxu Da
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, China
- Department of Surgical Oncology, Gansu Provincial Hospital, Lanzhou, China
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Babaei Z, Keyvanloo Shahrestanaki M, Aghaei M. MiR-1236: Key controller of tumor development and progression: Focus on the biological functions and molecular mechanisms. Pathol Res Pract 2023; 248:154671. [PMID: 37418995 DOI: 10.1016/j.prp.2023.154671] [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: 05/24/2023] [Accepted: 07/02/2023] [Indexed: 07/09/2023]
Abstract
Combating with the cancer, as one of the leading causes of morbidity and mortality worldwide, scientific community extensively evidenced microRNA 1236 (miR-1236) roles in the pathogenesis of malignant tumors. It has been mentioned that miR-1236 target genes and signal pathways that are key controller of tumor development and progression. Consistently, increasing evidence reports that miR-1236 participates in cancer cell growth, migration, invasion, apoptosis, and drug resistance, as well as tumor diagnosis, and prognosis. MiR-1236 is also implicated in epithelial-mesenchymal transition (EMT), which is a significant indicator of the metastatic process. Moreover, miR-1236 itself is regulated by several newly discovered long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs). Current review aimed to summarize and discuss different dimensions of miR-1236 involvement in the fundamental cellular and molecular mechanisms of tumor progressions. We believe that miR-1236 may serve as a non-invasive diagnostic marker and potential therapeutic target for cancer.
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Affiliation(s)
- Zeinab Babaei
- Department of Clinical Biochemistry and Biophysics, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran
| | | | - Mahmoud Aghaei
- Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.
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Lin Z, Li P, Tang Y, Tan H, Luo L. Hsa_circ_0007292 promotes chondrocyte injury in osteoarthritis via targeting the miR-1179/HMGB1 axis. J Orthop Surg Res 2023; 18:544. [PMID: 37516834 PMCID: PMC10386318 DOI: 10.1186/s13018-023-04026-7] [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: 04/11/2023] [Accepted: 07/17/2023] [Indexed: 07/31/2023] Open
Abstract
BACKGROUND Circular RNAs (circRNAs) have been demonstrated to participate in the progression of osteoarthritis (OA). This study aimed to investigate the role and molecular mechanism of hsa_circ_0007292 in OA. METHODS Hsa_circ_0007292 was identified by analyzing a circRNA microarray from the Gene Expression Omnibus (GEO) database, and its expression was detected by real-time PCR in OA cartilage tissues and interleukin (IL)-1β-induced two human chondrocytes (CHON-001 and C28/I2), the OA cell models. The effects of hsa_circ_0007292 knockdown and miR-1179 overexpression on IL-1β-induced chondrocyte injury were examined by CCK-8, BrdU, flow cytometry, ELISA, and western blot. RNA pull-down assay and dual-luciferase reporter gene assay were used to analyze the interaction between hsa_circ_0007292 and miR-1179. Rescue experiments were carried out to determine the correlations among hsa_circ_0007292, miR-1179 and high mobility group box-1 (HMGB1). RESULTS Hsa_circ_0007292 expression was upregulated in OA tissues and IL-1β-induced chondrocytes. Both downregulation of hsa_circ_0007292 and miR-1179 overexpression increased the proliferation and Aggrecan expression, suppressed apoptosis, matrix catabolic enzyme MMP13 expression and inflammatory factor (TNF-α, IL-6, and IL-8) levels. There was a negative correlation between hsa_circ_0007292 and miR-1179, and a positive correlation between hsa_circ_0007292 and HMGB1 in OA tissues. The mechanistic study showed that hsa_circ_0007292 prevented HMGB1 downregulation by sponging miR-1179. Upregulation of HMGB1 could reverse the influence of hsa_circ_0007292 downregulation on IL-1β-induced chondrocyte injury. CONCLUSIONS Downregulation of hsa_circ_0007292 relieved apoptosis, extracellular matrix degradation and inflammatory response in OA via the miR-1179/HMGB1 axis, suggesting that hsa_circ_0007292 might be a potential therapeutic target for OA treatment.
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Affiliation(s)
- Zhiping Lin
- Orthopedic Center, The Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, China
| | - Peng Li
- Stem Cell Research and Cellular Therapy Center, The Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, China
| | - Yangyang Tang
- The Marine Biomedical Research Institute, Guangdong Medical University, No.2, Wenming East Road, Zhanjiang, 524023, China
| | - Hongchang Tan
- Orthopedic Center, The Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, China
| | - Lianxiang Luo
- The Marine Biomedical Research Institute, Guangdong Medical University, No.2, Wenming East Road, Zhanjiang, 524023, China.
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10
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Liang D, Liu H, Yang Q, He Y, Yan Y, Li N, You W. Retracted: Long noncoding RNA RHPN1-AS1, induced by KDM5B, is involved in breast cancer via sponging miR-6884-5p. J Cell Biochem 2023; 124:1064. [PMID: 32003509 DOI: 10.1002/jcb.29645] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2019] [Accepted: 12/09/2019] [Indexed: 12/24/2022]
Abstract
The above article, published online in Journal of Cellular Biochemistry on 31 January 2020 in Wiley Online Library (https://doi.org/10.1002/jcb.29645), has been retracted by agreement between the authors, the journal's Editor in Chief, Prof. Dr. Christian Behl, and Wiley Periodicals LLC. The authors asked to retract their article after substantial mistakes in experimental data were found, thus the results are considered to be invalid.
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Affiliation(s)
- Dong Liang
- Department of Breast Surgery, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, Zhengzhou, Henan, China
| | - Hui Liu
- Department of Breast Surgery, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, Zhengzhou, Henan, China
| | - Qinheng Yang
- Department of Breast Surgery, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, Zhengzhou, Henan, China
| | - Yaning He
- Department of Breast Surgery, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, Zhengzhou, Henan, China
| | - Yuan Yan
- Department of Breast Surgery, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, Zhengzhou, Henan, China
| | - Na Li
- Department of Breast Surgery, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, Zhengzhou, Henan, China
| | - Wei You
- Department of Breast Surgery, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, Zhengzhou, Henan, China
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Zhang J, Li J, Xiong Y, Li R. Circ_0000284 upregulates RHPN2 to facilitate pancreatic cancer proliferation, metastasis, and angiogenesis through sponging miR-1179. J Biochem Mol Toxicol 2023; 37:e23274. [PMID: 36536496 DOI: 10.1002/jbt.23274] [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: 11/30/2021] [Revised: 08/15/2022] [Accepted: 12/02/2022] [Indexed: 12/24/2022]
Abstract
BACKGROUND Circular RNA (circRNA) has been confirmed to be a key regulator for pancreatic cancer (PC) progression, but the role of circ_0000284 in PC development remains unclear. METHODS Quantitative real-time PCR was used to measure the expression of circ_0000284, microRNA (miR)-1179, and rhophilin 2 (RHPN2). PC cell proliferation, metastasis, angiogenesis, and apoptosis were assessed by EdU assay, transwell assay, tube formation assay, and flow cytometry. Relative protein expression was determined by western blot analysis. The interaction between miR-1179 and circ_0000284 or RHPN2 was confirmed by dual-luciferase reporter assay and RNA pull-down assay. RESULTS Circ_0000284 was significantly upregulated in PC tissues and cells, and its knockdown inhibited PC cell proliferation, migration, invasion, and angiogenesis while promoting apoptosis. MiR-1179 was downregulated in PC tissues and cells, and it could be sponged by circ_0000284. Moreover, the miR-1179 inhibitor reversed the regulation of circ_0000284 knockdown on PC cell progression. The highly expressed RHPN2 was found in PC tissues and cells, and it could be targeted by miR-1179. Also, circ_0000284 sponged miR-1179 to regulate RHPN2 expression. Overexpressed RHPN2 could reverse the regulation of circ_0000284 knockdown on PC cell progression. In addition, interference of circ_0000284 was discovered to repress PC tumor growth by regulating miR-1179/RHPN2.RHPN2. CONCLUSION To sum up, our data confirmed that circ_0000284 facilitated PC malignant progression depending on the regulation of miR-1179/RHPN2 axis, suggesting that circ_0000284 might be a potential target for PC treatment.
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Affiliation(s)
- Jian Zhang
- Department of Geratic Gastroenterological Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Jiangwei Li
- Department of Geratic Gastroenterological Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Yongqiang Xiong
- Department of Geratic Gastroenterological Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Ren Li
- Department of Geratic Gastroenterological Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
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12
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Xiao X, Xi X, Xiao S, Ni J. Circ_0101622 governs the miR-1179/RAB23 pathway to promote the aggressive progression of thyroid cancer. Mol Cell Toxicol 2022. [DOI: 10.1007/s13273-022-00236-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
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13
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Shen Q, Li J, Pan X, Zhang C, Jiang X, Li Y, Chen Y, Pang B. An immune-related microRNA signature prognostic model for pancreatic carcinoma and association with immune microenvironment. Sci Rep 2022; 12:9123. [PMID: 36056032 PMCID: PMC9440256 DOI: 10.1038/s41598-022-13045-z] [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: 02/09/2022] [Accepted: 05/19/2022] [Indexed: 11/09/2022] Open
Abstract
To establish a prognostic model based on immune-related microRNA (miRNA) for pancreatic carcinoma. Weighted correlation network analysis (WGCNA) was performed using the "WGCNA" package to find the key module genes involved in pancreatic carcinoma. Spearman correlation analysis was conducted to screen immune-related miRNAs. Uni- and multi-variate COX regression analyses were carried out to identify miRNAs prognostic for overall survival (OS) of pancreatic carcinoma, which were then combined to generate a prognostic model. Kaplan–Meier survival analysis, receiver operating characteristic (ROC) analysis, distribution plot of survival status in patients and regression analysis were collectively performed to study the accuracy of the model in prognosis. Target genes of the miRNAs in the model were intersected with the key module genes, and a miRNA–mRNA network was generated and visualized by Cytoscape3.8.0. TIMER analysis was conducted to study the abundance of immune infiltrates in tumor microenvironment of pancreatic carcinoma. Expression levels of immune checkpoint genes in subgroups stratified by the model were compared by Wilcoxon test. Gene Set Enrichment Analysis (GSEA) was performed to analyze the enriched signaling pathways between subgroups. Differential analysis revealed 1826 genes differentially up-regulated in pancreatic carcinoma and 1276 genes differentially down-regulated. A total of 700 immune-related miRNAs were obtained, of which 7 miRNAs were significantly associated with OS of patients and used to establish a prognostic model with accurate predictive performance. There were 99 mRNAs overlapped from the 318 target genes of the 7 miRNAs and the key modules genes analyzed by WGCNA. Patient samples were categorized as high or low risk according to the prognostic model, which were significantly associated with dendritic cell infiltration and expression of immune checkpoint genes (TNFSF9, TNFRSF9, KIR3DL1, HAVCR2, CD276 and CD80). GSEA showed remarkably enriched signaling pathways in the two subgroups. This study identified an immune-related 7-miRNA based prognostic model for pancreatic carcinoma, which could be used as a reliable tool for prognosis.
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Affiliation(s)
- Qian Shen
- Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - JunChen Li
- Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Xue Pan
- Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - ChuanLong Zhang
- Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - XiaoChen Jiang
- Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Yi Li
- Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Yan Chen
- International Medical Department of Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
| | - Bo Pang
- International Medical Department of Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
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14
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Chen Y. Role of miR-720 in prognosis and progression of gastric cancer. Shijie Huaren Xiaohua Zazhi 2022; 30:349-355. [DOI: 10.11569/wcjd.v30.i8.349] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Gastric cancer is a common malignant tumor of the digestive system with a high incidence and poor prognosis. Due to the lack of effective markers, patients are always diagnosed at an advanced stage and miss the best chance for treatment. The function of miR-720 in other malignancies has been widely reported, but its specific role in the development of gastric cancer remains unknown.
AIM To evaluate the value of miR-720 in the prognosis and tumor progression of gastric cancer, by analyzing its expression level and biological effect in gastric cancer.
METHODS The expression level of miR-720 was analyzed by real-time quantitative PCR, the prognostic value of miR-720 was evaluated by Kaplan-Meier and Cox regression analysis, and the proliferation, metastasis, and invasion of gastric cancer cells with down-regulated expression of miR-720 were analyzed by CCK-8 and Transwell assays.
RESULTS The expression of miR-720 was down-regulated in gastric cancer tissues and cell lines, which was significantly associated with TNM stage and poor prognosis of patients (P < 0.05). MiR-720 expression and TNM stage were identified as independent prognostic factors for gastric cancer, and down-regulated expression of miR-720 promoted the proliferation, metastasis, and invasion of gastric cancer cells.
CONCLUSION MiR-720 may be involved in the progression of gastric cancer and provide a new therapeutic target for the treatment of this malignancy.
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Affiliation(s)
- Ying Chen
- Department of GI Medicine, Zhuji Central Hospital, Zhuji 311899, Zhejiang Province, China
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15
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Circ_0000263 facilitates the proliferation and inhibits the apoptosis of cervical cancer depending on the regulation of miR-1179/ABL2 axis. Reprod Sci 2022; 29:2636-2646. [PMID: 35355231 DOI: 10.1007/s43032-022-00920-3] [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: 11/30/2021] [Accepted: 03/12/2022] [Indexed: 12/09/2022]
Abstract
Circular RNA (circRNA) has been reported to participate in the progression of cervical cancer (CC). Studies on the role and mechanism of circ_0000263 in CC are limited, and more studies are needed. The expression of circ_0000263, microRNA (miR)-1179 and ABL proto-oncogene 2 (ABL2) mRNA in tissues and cells was analyzed by quantitative real-time PCR. The proliferation and apoptosis of CC cells were determined using cell counting kit 8 assay, Edu assay, colony formation assay and flow cytometry. The protein expression of proliferation markers, apoptosis markers and ABL2 was detected by western blot analysis. The interaction between RNAs was estimated via dual-luciferase reporter assay. Xenograft models were applied to explore the effect of circ_0000263 knockdown on CC tumorigenesis. Circ_0000263 was highly expressed in CC tumor tissues. Silencing of circ_0000263 suppressed CC cell proliferation and increased apoptosis. Circ_0000263 served as a sponge for miR-1179, and miR-1179 inhibitor reversed the regulation of si-circ_0000263 on CC cell proliferation and apoptosis. ABL2 could be targeted by miR-1179, and circ_0000263 could sponge miR-1179 to regulate ABL2. Overexpression of ABL2 reversed the anti-proliferation and pro-apoptosis roles of miR-1179 in CC cells. In addition, circ_0000263 knockdown reduced CC tumor growth by miR-1179/ABL2 axis. In brief, the results demonstrated that circ_0000263 exerted an oncogene role in CC, which suggested that circ_0000263 might be a promising therapeutic target for CC.
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16
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Chen AX, Jin RY, Zhou WM, Ye YJ, Lu JL, Ren YF, Xuan FL. CircRNA circ_0043533 facilitates cell growth in polycystic ovary syndrome by targeting miR-1179. Reprod Biol 2022; 22:100637. [PMID: 35338913 DOI: 10.1016/j.repbio.2022.100637] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Revised: 03/09/2022] [Accepted: 03/11/2022] [Indexed: 10/18/2022]
Abstract
Increasing evidence indicates that circular RNAs (CircRNAs) have an important role in human diseases, including polycystic ovary syndrome (PCOS). Recently, circ_0043533, a novel circRNA, was proposed to be involved in the progression of PCOS. However, its role in PCOS has not been explored. In this study, the expression levels of circ_0043533 and miR-1179 in ovarian granulosa cells (OGCs) were examined by qRT-PCR analysis. Moreover, knockdown of circ_0043533 in OGC lines COV434 and KGN, respectively, the cell viability, proliferation, apoptosis, and cycle-related markers of insulin-triggered OGCs were examined by CCK-8, EdU staining, flow cytometry, and western blot assays, respectively. The interaction between circ_0043533 and miR-1179 was examined by bioinformatics, dual-luciferase assay, and RNA immunoprecipitation. Besides, effects of the miR-1179 inhibitor on cell viability and apoptosis in OGC lines with circ_0043533 knockdown were also evaluated. OGCs and insulin-treated OGCs exhibited higher circ_0043533 levels in comparison to the IOSE80 cells. Additionally, knockdown of circ_0043533 remarkably inhibited the cell viability and proliferation and promoted the apoptosis of insulin-treated COV434 and KGN cells, respectively. Meanwhile, circ_0043533 knockdown could down-regulate the Bcl-2, CDK2, and Cyclin D1 expressions, and up-regulate the Bax levels. Furthermore, we demonstrated that circ_0043533 acted as a sponge to absorb miR-1179. Interestingly, miR-1179 inhibition remarkably attenuated the effect of circ_0043533 silence on cell proliferation and apoptosis in insulin-treated COV434 and KGN cells. Taken together, this study revealed that circ_0043533 knockdown restrained the malignant progression of PCOS via targeting miR-1179. Our data suggested that circ_0043533 would serve as a novel therapeutic target for PCOS.
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Affiliation(s)
- Ai-Xue Chen
- Department of Gynecology, Changxing People's Hospital of Chongming District, Shanghai, China
| | - Rui-Ying Jin
- Department of Gynecology, Jiaojiang Maternal and Child Health Hospital, Taizhou City, Zhejiang, China
| | - Wei-Mei Zhou
- Department of Ultrasound, Jiaojiang Maternal and Child Health Hospital, Taizhou City, Zhejiang, China
| | - Yong-Ju Ye
- Department of Gynaecology, Lishui Hospital of Traditional Chinese Medicine, Lishui, Zhejiang, China
| | - Jia-Li Lu
- Department of Gynecology, Huzhou Maternity & Child Health Care Hospital, Huzhou, Zhejiang, China
| | - Yue-Fang Ren
- Department of Gynecology, Huzhou Maternity & Child Health Care Hospital, Huzhou, Zhejiang, China
| | - Fei-Lan Xuan
- Department of Gynecology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
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17
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Jia Z, Tang X, Zhang X, Shen J, Sun Y, Qian L. miR-153-3p Attenuates the Development of Gastric Cancer by Suppressing SphK2. Biochem Genet 2022; 60:1748-1761. [PMID: 35088224 DOI: 10.1007/s10528-021-10166-4] [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: 08/30/2021] [Accepted: 12/06/2021] [Indexed: 01/04/2023]
Abstract
Gastric cancer (GC) is the second leading cause of cancer-related mortality worldwide. MicroRNAs (miRNAs) have been extensively reported to play a role in GC development; however, it remains unknown whether miR-153-3p participates in the nosogenesis of GC. GC tissues along with the adjacent nontumor tissues were obtained from 50 patients with GC. Moreover, we incubated human GC cell lines (SGC7901, AGS, MGC803, and BGC823) and a gastric epithelial cell line (GES-1) and then transfected BGC823 cells with miR-153-3p and DNA/SphK2 vector to determine the action of miR-153-3p and SphK2 on GC. RT-qPCR was performed to determine the levels of miR-153-3p and sphingosine kinase 2 (SphK2). The viability of BGC823 cells was measured by the CCK-8 assay, while wound healing assays and transwell assays were used to measure the migration and invasion ability of BGC823 cells. Western blotting analysis and immunohistochemistry (IHC) were conducted to evaluate the level of SphK2. The binding ability of miR-153-3p and SphK2 was determined by dual-luciferase reporter assays. The expression level of miR-153-3p was reduced in GC tissues and cells, while the SphK2 was enhanced. An increase in miR-153-3p level led to a decline in the growth and metastasis of GC cells and increased their apoptosis. Moreover, a decrease in miR-153-3p level elevated GC cells growth and metastasis, and attenuated their apoptosis. SphK2 was also corroborated as a downstream gene of miR-153-3p. Here, SphK2 expression was elevated in GC tissues and cells, indicating SphK2 might be involved in the development of GC. Rescue assays showed that miR-153-3p could reverse the effect of SphK2 on the cell growth, metastasis, and the apoptosis of GC cells. In conclusion, this study showed that miR-153-3p suppressed the growth and metastasis in GC cells by regulating SphK2, which might facilitate the search for novel biomarkers to treat GC.
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Affiliation(s)
- Zhengwo Jia
- Department of Digestive System, Tongxiang First People's Hospital, 1918, Jiaochang East Road, Tongxiang, 314500, Zhejiang, China
| | - Xiaofang Tang
- Department of Digestive System, Tongxiang First People's Hospital, 1918, Jiaochang East Road, Tongxiang, 314500, Zhejiang, China
| | - Xicheng Zhang
- Department of Digestive System, Tongxiang First People's Hospital, 1918, Jiaochang East Road, Tongxiang, 314500, Zhejiang, China
| | - Jingen Shen
- Department of Digestive System, Tongxiang First People's Hospital, 1918, Jiaochang East Road, Tongxiang, 314500, Zhejiang, China
| | - Yuanlong Sun
- Department of Digestive System, Tongxiang First People's Hospital, 1918, Jiaochang East Road, Tongxiang, 314500, Zhejiang, China
| | - Lifen Qian
- Department of Digestive System, Tongxiang First People's Hospital, 1918, Jiaochang East Road, Tongxiang, 314500, Zhejiang, China.
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18
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Ji Z, Diao W, Shang J. Circular RNA circ_0000592 elevates ANXA4 expression via sponging miR-1179 to facilitate tumor progression in gastric cancer. Anticancer Drugs 2022; 33:e644-e654. [PMID: 34459457 DOI: 10.1097/cad.0000000000001216] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Increasing evidence indicated that dysregulated circular RNAs were implicated in the progression of multiple malignancies. However, the function of circ_0000592 in gastric cancer (GC) progression and its associated mechanism remain poorly understood. Quantitative real-time PCR and Western blot assay were performed to detect RNA and protein expression. Cell proliferation, migration and invasion were analyzed by 5-Ethynyl-2'-deoxyuridine staining assay, Transwell migration assay and Transwell invasion assay, respectively. The glucose/lactate assay kit was used to assess the rates of glucose consumption and lactate production. The interaction between microRNA-1179 (miR-1179) and circ_0000592 or Annexin A4 (ANXA4) was confirmed by dual-luciferase reporter assay and RNA pull-down assay. Xenograft tumor model was established to investigate the effect of circ_0000592 on tumor growth in vivo. Circ_0000592 expression was elevated in GC tissues and cells. Circ_0000592 knockdown hampered cell proliferation, migration, invasion and glycolysis of GC cells. MiR-1179 was a direct target of circ_0000592, and circ_0000592 silencing-mediated effects in GC cells were partly reversed by the knockdown of miR-1179. MiR-1179 interacted with the 3' untranslated region (3'UTR) of ANXA4. Circ_0000592 silencing reduced ANXA4 expression partly by upregulating miR-1179 in GC cells. ANXA4 overexpression partly overturned circ_0000592 knockdown-induced effects in GC cells. Circ_0000592 depletion markedly suppressed xenograft tumor growth in vivo. Circ_0000592 contributed to GC progression through regulating miR-1179/ANXA4 axis, which provided novel potential biomarkers and therapeutic targets for GC treatment.
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Affiliation(s)
| | | | - Jincai Shang
- General Surgical, First Affiliated Hospital of Jiamusi University, Jiamusi, Heilongjiang, China
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19
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CircFOXM1 promotes proliferation and metastasis of hepatocellular carcinoma via regulating miR-1179/SPAG5 axis. Sci Rep 2021; 11:23890. [PMID: 34903799 PMCID: PMC8668908 DOI: 10.1038/s41598-021-03285-w] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2021] [Accepted: 11/24/2021] [Indexed: 12/24/2022] Open
Abstract
Hepatocellular carcinoma (HCC) predominantly occurs in patients with chronic liver disease, accounting for 70-90% of all liver cancer cases. The role of circFOXM1/miR-1179/SPAG5 axis in HCC has not been reported. This study aimed to explore the regulatory mechanism of circFOXM1 in HCC proliferation and metastasis. RNA polymerase inhibitor actinomycin D and RNase R exonuclease were used to identify circFOXM1 in HCC cells. The qRT-PCR was used to detect circFOXM1 expression. Specific siRNA for circFOXM1 was designed, and the sequence of circFOXM1 was inserted in pLCDH-ciR to overexpress circFOXM. Cell proliferation was detected by CCK8 in vitro, by tumor volume and tumor weight of HCC xenograft in vivo. Cell migration was detected by transwell test. Binding status of circFOXM1 with miR-1179 was detected by luciferase reporter gene assay. Rescue experiments were applied to identify the oncogenic mechanism of circFOXM1 in HCC cells. Actinomycin D assay confirmed the cyclization of circFOXM1. RNase R treatment showed that circFOXM1 was not affected by RNase R exonuclease. CCK8 assay, tumor volume and tumor weight showed that circFOXM1 effectively promoted HCC cell proliferation. Transwell assay showed that circFOXM effectively promoted migration and invasion abilities of HCC cells. Luciferase reporter gene activity assay showed that miR-1179 had complementary binding sites with circFOXM1 and SPAG5. CircFOXM1 silencing inhibited malignant phenotypes in HCC cells were partly rescued by either miR-1179 silencing or SPAG5 overexpression. CircFOXM1 promoted HCC cell proliferation and metastasis by regulating miR-1179/SPAG5 axis.
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20
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Sui Z, Sui X. Long non-coding RNA TMPO-AS1 promotes cell proliferation, migration, invasion and epithelial-to-mesenchymal transition in gallbladder carcinoma by regulating the microRNA-1179/E2F2 axis. Oncol Lett 2021; 22:855. [PMID: 34777589 PMCID: PMC8581476 DOI: 10.3892/ol.2021.13116] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Accepted: 09/19/2021] [Indexed: 12/29/2022] Open
Abstract
Gallbladder carcinoma (GBC), which is a common tumor of the biliary system, poses a serious threat to human life and health. The present study aimed to investigate the molecular mechanism of the long non-coding (lnc)RNA thymopoietin antisense transcript 1 (TMPO-AS1)/microRNA (miRNA/miR)-1179/E2F transcription factor 2 (E2F2) axis in GBC. The viability, proliferation, migration, invasion and epithelial-to-mesenchymal transition (EMT) of GBC cell lines were assessed via the Cell Counting Kit-8, colony formation, Transwell migration and invasion, immunofluorescence and western blot assays. In the present study, lncRNA TMPO-AS1 was significantly upregulated in clinical GBC tissues and cell lines, and was highly expressed in stage III+IV patients with GBC compared with stage I+II patients with GBC. In addition, the overall survival rate of patients with low TMPO-AS1 expression levels was higher than those with high TMPO-AS1 expression levels. Furthermore, TMPO-AS1 knockdown inhibited the viability, proliferation, migration, invasion and EMT of GBC cell lines. In addition, miR-1179 expression was downregulated in clinical GBC tissues and cell lines, and negatively correlated with TMPO-AS1 expression. The results revealed that miR-1179 is a target of TMPO-AS1, which was confirmed via the dual-luciferase reporter assay and RNA pull-down analysis. Overexpression of miR-1179 inhibited the viability, proliferation, migration, invasion and EMT of GBC cell lines. Furthermore, E2F2 was verified as a direct target of miR-1179 by binding to its 3'-untranslated region. E2F2 expression was significantly upregulated in clinical GBC tissues and cell lines, and negatively correlated with miR-1179 expression. Notably, E2F2 knockdown partially hindered the effects of TMPO-AS1/miR-1179 on the proliferation and metastasis of GBC cell lines. Taken together, the results of the present study suggest that TMPO-AS1 potentially plays a tumor-promoting role in the occurrence and development of GBC, which may be achieved by regulating the miR-1179/E2F2 axis.
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Affiliation(s)
- Zhenghui Sui
- Department of General Surgery, The People's Hospital of Danyang and Affiliated Danyang Hospital of Nantong University, Danyang, Jiangsu 212300, P.R. China
| | - Xin Sui
- Department of General Surgery, The People's Hospital of Danyang and Affiliated Danyang Hospital of Nantong University, Danyang, Jiangsu 212300, P.R. China
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21
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Li H, Zhang Y, Song H, Li L. CircRFX3 contributes to glioma progression through the circRFX3-miR-1179/miR-1229-VASP axis. Cancer Cell Int 2021; 21:588. [PMID: 34727925 PMCID: PMC8561884 DOI: 10.1186/s12935-021-02293-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2021] [Accepted: 10/21/2021] [Indexed: 01/07/2023] Open
Abstract
Background Circular RNAs (circRNAs) are implicated in the carcinogenesis of human cancers. However, the functional roles of circRFX3 in glioma are not elucidated. Methods Quantitative real-time polymerase chain reaction (qRT-PCR) assay was performed for the levels of circRFX3, RFX3, miR-1179, miR-1229 and vasodilator stimulated phosphoprotein (VASP). Actinomycin D assay and RNase R assay were employed to analyze the characteristics of circRFX3. Cell Counting Kit-8 (CCK-8) assay and colony formation assay were conducted for cell proliferation. Transwell assay was used for cell migration and invasion. Flow cytometry analysis was adopted for cell apoptosis. RNA pull-down assay, dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were employed to analyze the interaction between miR-1179/miR-1229 and circRFX3 or VASP. Western blot assay was conducted for VASP protein level. Murine xenograft model assay was used to investigate the role of circRFX3 in vivo. Results CircRFX3 level was increased in glioma tissues and cells. Knockdown of circRFX3 suppressed glioma cell proliferation, migration and invasion and promoted apoptosis in vitro and repressed tumorigenesis of glioma in vivo. MiR-1179 and miR-1229 were identified to be the targets of circRFX3. MiR-1179 or miR-1229 inhibition reversed the impacts of circRFX3 knockdown on glioma cell malignant behaviors. Additionally, VASP was demonstrated to be the target gene of miR-1179 and miR-1229, and VASP overexpression abolished the effect of circRFX3 knockdown on glioma cell progression. Conclusion CircRFX3 served as a tumor promoter in glioma via modulating miR-1179/miR-1229-VASP axis, which might provide a novel target for glioma therapy.
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Affiliation(s)
- Hongli Li
- Department of Neurology, Huaihe Hospital, Henan University, Kaifeng, Henan, China
| | - Yiwei Zhang
- School of Nursing and Health, North Section of Jinming Avenue, Henan University, Kaifeng, 475001, Henan, China
| | - Huiqin Song
- Department of Pathology, The First Affiliated Hospital of Henan University, Kaifeng, Henan, China
| | - Li Li
- School of Nursing and Health, North Section of Jinming Avenue, Henan University, Kaifeng, 475001, Henan, China.
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22
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Li J, Ma J, Huang S, Li J, Zhou L, Sun J, Chen L. WITHDRAWN: Circ-LAMP2 regulates aortic smooth muscle cell proliferation and apoptosis in thoracic aortic aneurysm via modulation of autophagy and NF-κB pathway. Hum Pathol 2021:S0046-8177(21)00161-1. [PMID: 34592240 DOI: 10.1016/j.humpath.2021.09.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Accepted: 09/02/2021] [Indexed: 10/20/2022]
Abstract
This article has been withdrawn at the request of the editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.
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Affiliation(s)
- Jun Li
- Department of Neurosurgery, Shanghai Fifth People's Hospital, Fudan University, Shanghai, 200240, China.
| | - Junfeng Ma
- Department of Neurosurgery, Shanghai Fifth People's Hospital, Fudan University, Shanghai, 200240, China
| | - Shan Huang
- Department of Neurosurgery, Shanghai Fifth People's Hospital, Fudan University, Shanghai, 200240, China
| | - Jun Li
- Department of Neurosurgery, Shanghai Fifth People's Hospital, Fudan University, Shanghai, 200240, China
| | - Liang Zhou
- Department of Neurosurgery, Shanghai Fifth People's Hospital, Fudan University, Shanghai, 200240, China
| | - Jiahua Sun
- Department of Neurosurgery, Shanghai Fifth People's Hospital, Fudan University, Shanghai, 200240, China
| | - Lin Chen
- Department of Neurosurgery, Shanghai Fifth People's Hospital, Fudan University, Shanghai, 200240, China
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23
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Guan B, Ma J, Yang Z, Yu F, Yao J. LncRNA NCK1-AS1 exerts oncogenic property in gastric cancer by targeting the miR-22-3p/BCL9 axis to activate the Wnt/β-catenin signaling. ENVIRONMENTAL TOXICOLOGY 2021; 36:1640-1653. [PMID: 33974352 DOI: 10.1002/tox.23160] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 04/14/2021] [Accepted: 04/23/2021] [Indexed: 06/12/2023]
Abstract
Long noncoding RNAs (lncRNAs) exert crucial effects on the development of many malignancies, including gastric cancer. Herein, we investigated the role of lncRNA noncatalytic region of tyrosine kinase adaptor protein 1 (NCK1) divergent transcript (NCK1-DT, also known as NCK1-AS1) in gastric cancer. Reverse transcription quantitative polymerase chain reaction demonstrated that NCK1-AS1 exhibited high expression in gastric cancer tissues and cells. In vitro assays including MTT, colony formation, Transwell, wound healing and sphere formation assays indicated that NCK1-AS1 depletion inhibited cell proliferation, migration, invasion and stemness maintenance. Luciferase reporter and RIP assays suggested that NCK1-AS1 functioned as a competitive endogenous RNA (ceRNA) for miR-22-3p to positively modulate BCL9 expression. BCL9 was a target gene of miR-22-3p. According to western blot analysis and TOP/FOP flash assay, NCK1-AS1 activated the Wnt/β-catenin signaling via the miR-22-3p/BCL9 axis. Furthermore, rescue experiments verified that NCK1-AS1 affected cellular processes by activating the Wnt/β-catenin signaling pathway via the miR-22-3p/BCL9 axis. Tumor xenograft model validated that NCK1-AS1 promoted tumor growth in vivo via the Wnt/β-catenin signaling by upregulating BCL9 expression. Overall, NCK1-AS1 functions as an oncogene and promotes gastric cancer progression via the miR-22-3p/BCL9-Wnt/β-catenin signaling pathway.
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Affiliation(s)
- Bugao Guan
- Department of General Surgery, Jinhu People's Hospital, Huaian, Jiangsu, China
| | - Jun Ma
- Department of General Surgery, Jinhu People's Hospital, Huaian, Jiangsu, China
| | - Zhi Yang
- Department of Gastroenterology, Jinhu People's Hospital, Huaian, Jiangsu, China
| | - Fei Yu
- Department of General Surgery, Jinhu People's Hospital, Huaian, Jiangsu, China
| | - Jian Yao
- Department of Gastroenterology, Jinhu People's Hospital, Huaian, Jiangsu, China
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24
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Lamberti MJ, Nigro A, Casolaro V, Rumie Vittar NB, Dal Col J. Damage-Associated Molecular Patterns Modulation by microRNA: Relevance on Immunogenic Cell Death and Cancer Treatment Outcome. Cancers (Basel) 2021; 13:cancers13112566. [PMID: 34073766 PMCID: PMC8197279 DOI: 10.3390/cancers13112566] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2021] [Revised: 05/14/2021] [Accepted: 05/18/2021] [Indexed: 02/06/2023] Open
Abstract
Simple Summary Inside the cell, damage-associated molecular pattern molecules (DAMPs) play several physiological functions, but when they are released or translocated to the extracellular space, they gain additional immunogenic roles. Thus, DAMPs are considered key hallmarks of immunogenic cell death (ICD) in cancer, a functionally unique regulated form of stress-mediated cell death that activates the immune system response against tumor cells. Several epigenetic modulators of DAMPs have been reported. In this review, we aimed to provide an overview of the effects of microRNAs (miRNAs) on the expression of DAMPs and the putative link between miRNA, DAMPs, and cell death, focused on ICD. Overall, we propose that miRNAs, by targeting DAMPs, play critical roles in the regulation of both cell death and immune-associated mechanisms in cancer, while evidence of their potential involvement in ICD is limited. Finally, we discuss emerging data regarding the impact of miRNAs’ modulation on cancer treatment outcome. Abstract Immunogenic cell death (ICD) in cancer is a functionally unique regulated form of stress-mediated cell death that activates both the innate and adaptive immune response against tumor cells. ICD makes dying cancer cells immunogenic by improving both antigenicity and adjuvanticity. The latter relies on the spatiotemporally coordinated release or exposure of danger signals (DAMPs) that drive robust antigen-presenting cell activation. The expression of DAMPs is often constitutive in tumor cells, but it is the initiating stressor, called ICD-inducer, which finally triggers the intracellular response that determines the kinetics and intensity of their release. However, the contribution of cell-autonomous features, such as the epigenetic background, to the development of ICD has not been addressed in sufficient depth. In this context, it has been revealed that several microRNAs (miRNAs), besides acting as tumor promoters or suppressors, can control the ICD-associated exposure of some DAMPs and their basal expression in cancer. Here, we provide a general overview of the dysregulation of cancer-associated miRNAs whose targets are DAMPs, through which new molecular mediators that underlie the immunogenicity of ICD were identified. The current status of miRNA-targeted therapeutics combined with ICD inducers is discussed. A solid comprehension of these processes will provide a framework to evaluate miRNA targets for cancer immunotherapy.
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Affiliation(s)
- María Julia Lamberti
- INBIAS, CONICET-UNRC, Río Cuarto, Córdoba 5800, Argentina;
- Department of Medicine, Surgery and Dentistry ‘Scuola Medica Salernitana’, University of Salerno, Baronissi, 84081 Salerno, Italy; (A.N.); (V.C.)
- Correspondence: (M.J.L.); (J.D.C.)
| | - Annunziata Nigro
- Department of Medicine, Surgery and Dentistry ‘Scuola Medica Salernitana’, University of Salerno, Baronissi, 84081 Salerno, Italy; (A.N.); (V.C.)
| | - Vincenzo Casolaro
- Department of Medicine, Surgery and Dentistry ‘Scuola Medica Salernitana’, University of Salerno, Baronissi, 84081 Salerno, Italy; (A.N.); (V.C.)
| | | | - Jessica Dal Col
- Department of Medicine, Surgery and Dentistry ‘Scuola Medica Salernitana’, University of Salerno, Baronissi, 84081 Salerno, Italy; (A.N.); (V.C.)
- Correspondence: (M.J.L.); (J.D.C.)
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Wang Y, Zong H, Zhou H. Circular RNA circ_0062389 modulates papillary thyroid carcinoma progression via the miR-1179/high mobility group box 1 axis. Bioengineered 2021; 12:1484-1494. [PMID: 33926347 PMCID: PMC8806330 DOI: 10.1080/21655979.2021.1914470] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023] Open
Abstract
Circular RNAs (circRNAs) feature prominently in regulating the progression of tumors, including papillary thyroid carcinoma (PTC). This work is designated to delve into the role of circ_0062389 in PTC. Generally, quantitative real-time polymerase chain reaction (qRT-PCR) was employed to detect circ_0062389, miR-1179 and high mobility group box 1 (HMGB1) mRNA expression levels. RNase R assay was used to verify the circular characteristics of circ_0062389. After circ_0062389 was knocked down in PTC cells, CCK-8 assay was adopted to determine cell viability. Wound healing assay was leveraged to probe cell migration. Besides, Western blot assay was executed to examine the expression levels of HMGB1 and epithelial-mesenchymal transformation (EMT)-related markers (E-cadherin and N-cadherin). Dual-luciferase reporter assay was performed to authenticate the targeting relationships between miR-1179 and circ_0062389, as well as miR-1179 and HMGB1. Here, this work proved that circ_0062389 was greatly up-regulated in PTC tissues and cell lines. The high expression of circ_0062389 was related to large tumor size and positive lymphatic metastasis. Knocking down circ_0062389 could inhibit the proliferation, migration and EMT process of PTC cells. Besides, miR-1179 was a downstream molecule of circ_0062389. Furthermore, miR-1179 inhibitors could partially reverse the above effect of knocking down circ_0062389 on PTC cells. It was also confirmed that HMGB1 was a direct target of miR-1179 and mediated the effects of circ_0062389 and miR-1179 in PTC. Altogether, circ_0062389 can adsorb miR-1179, and regulate HMGB1 expression, thus playing a role in PTC.
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Affiliation(s)
- Yujuan Wang
- Otorhinolaryngology Head and Neck Surgery, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi, China
| | - Huafeng Zong
- Department of Pathology, Dalian Friendship Hospital, Dalian, Liaoning, China
| | - Haicheng Zhou
- Department of Endocrinology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China
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26
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Molecular targeted treatment and drug delivery system for gastric cancer. J Cancer Res Clin Oncol 2021; 147:973-986. [PMID: 33550445 DOI: 10.1007/s00432-021-03520-x] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2020] [Accepted: 01/10/2021] [Indexed: 12/24/2022]
Abstract
Gastric cancer is still a major cancer worldwide. The early diagnosis rate of gastric cancer in most high incidence countries is low. At present, the overall treatment effect of gastric cancer is poor, and the median overall survival remains low. Most of the patients with gastric cancer are in an advanced stage when diagnosed, and drug treatment has become the main means. Thus, new targeted drugs and therapeutic strategies are the hope of improving the therapeutic effect of gastric cancer. In this review, we summarize the new methods and advances of targeted therapy for gastric cancer, including novel molecular targeted therapeutic agents and drug delivery systems, with a major focus on the development of drug delivery systems (drug carriers and targeting peptides). Elaborating these new methods and advances will contribute to the management of gastric cancer.
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27
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Tang T, Wang S, Cai T, Cheng Z, Meng Y, Qi S, Zhang Y, Qi Z. High mobility group box 1 regulates gastric cancer cell proliferation and migration via RAGE-mTOR/ERK feedback loop. J Cancer 2021; 12:518-529. [PMID: 33391448 PMCID: PMC7739007 DOI: 10.7150/jca.51049] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2020] [Accepted: 10/30/2020] [Indexed: 12/16/2022] Open
Abstract
Gastric cancer (GC) is a common malignancy tumour in China. Despite various therapeutic approaches to improve the survival rate of GC patients, the effectiveness of currently available treatments remains unsatisfactory. High mobility group box 1 (HMGB1) is reported to play a role in tumour development. However, the molecular mechanisms involved in HMGB1-mediated regulation of proliferation and migration of GC cells remain unclear. In the present study, we demonstrated that HMGB1 is highly expressed in GC cells and tissue. In HGC-27 GC cells, HMGB1 overexpression or HMGB1 RNA interference both demonstrated that HMGB1 could promote GC cell proliferation and migration. Investigation of the underlying molecular mechanisms revealed that HMGB1 enhanced cyclins expression, induced epithelial-to-mesenchymal transition and matrix metalloproteinase (MMPs) expression and promoted RAGE expression as well as RAGE-mediated activation of Akt/mTOR/P70S6K and ERK/P90RSK/CREB signalling pathways. We also found that inhibition of ERK and mTOR using specific inhibitors reduced recombinant human HMGB1-induced RAGE expression, suggesting that the RAGE-mTOR/ERK positive feedback loop is involved in HMGB1-induced GC cell proliferation and migration. Our study highlights a novel mechanism by which HMGB1 promotes GC cell proliferation and migration via RAGE-mediated Akt-mTOR and ERK-CREB signalling pathways which also involves the RAGE-mTOR/ERK feedback loop. These findings indicate that HMGB1 is a potential therapeutic target for GC.
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Affiliation(s)
- Tuo Tang
- Department of Biochemistry and Molecular Biology.,Anhui Province Key Laboratory of Active Biological Macro-molecules
| | - Shengnan Wang
- Department of Biochemistry and Molecular Biology.,Anhui Province Key Laboratory of Active Biological Macro-molecules
| | - Tianyu Cai
- School of Clinical Medicine, Wannan Medical College, Wuhu, Anhui 241002, P.R. China
| | - Zhenyu Cheng
- School of Clinical Medicine, Wannan Medical College, Wuhu, Anhui 241002, P.R. China
| | - Yu Meng
- Department of Biochemistry and Molecular Biology.,Anhui Province Key Laboratory of Active Biological Macro-molecules
| | - Shimei Qi
- Department of Biochemistry and Molecular Biology.,Anhui Province Key Laboratory of Active Biological Macro-molecules
| | - Yao Zhang
- Department of Biochemistry and Molecular Biology.,Anhui Province Key Laboratory of Active Biological Macro-molecules
| | - Zhilin Qi
- Department of Biochemistry and Molecular Biology.,Anhui Province Key Laboratory of Active Biological Macro-molecules
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28
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Shen H, Xu L, You C, Tang H, Wu H, Zhang Y, Xie M. miR-665 is downregulated in glioma and inhibits tumor cell proliferation, migration and invasion by targeting high mobility group box 1. Oncol Lett 2020; 21:156. [PMID: 33552274 DOI: 10.3892/ol.2020.12417] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2019] [Accepted: 10/22/2020] [Indexed: 12/19/2022] Open
Abstract
Glioma is the most common brain tumor in adults. microRNAs (miRNAs/miRs) play an essential role in tumor development and progression. The present study aimed to investigate the potential clinical significance and function of miR-665 in glioma. Reverse transcription-quantitative PCR analysis was used to detect the expression of miR-665 in glioma tissues and cells. Survival curves were constructed using the Kaplan-Meier method. Cox regression analysis was performed to investigate the prognostic significance of miR-665. Cell Counting Kit-8 and Transwell assays were used to evaluate the role of miR-665 in glioma. Bioinformatics analysis and Dual-luciferase reporter assays were used to predict the putative direct targets of miR-665. Western blotting was used to evaluate the activity of the Wnt/β-catenin pathway. The relative expression of miR-665 was decreased in glioma tissues and cells and this downregulation was significantly associated with the Karnofsky performance scale score and World Health Organisation grade. Patients with glioma with low miR-665 expression had a shorter overall survival time compared with the high expression group. Besides, overexpression of miR-665 suppressed the proliferation, migration and invasion of glioma cells, while knockdown of miR-665 promoted these cellular behaviors. High mobility group box (HMGB)1 was a direct target of miR-665. It was also demonstrated that miR-665 may suppress glioma progression by targeting HMGB1 and inhibiting the Wnt/β-catenin pathway. Taken together, these data suggested that miR-665 may have a tumor suppressor role in glioma by targeting HMGB1. Therefore, miR-665 may be a novel prognostic biomarker and the miR-665/HMGB1 axis may be a novel therapeutic target for the treatment of glioma.
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Affiliation(s)
- Hao Shen
- Department of Neurosurgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563003, P.R. China
| | - Ling Xu
- Department of Neurosurgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563003, P.R. China
| | - Chunyue You
- Department of Neurosurgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563003, P.R. China
| | - Huaibo Tang
- Department of Neurosurgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563003, P.R. China
| | - Haitao Wu
- Department of Neurosurgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563003, P.R. China
| | - Yong Zhang
- Department of Neurosurgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563003, P.R. China
| | - Mingxiang Xie
- Department of Neurosurgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563003, P.R. China
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29
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Xue J, Suarez JS, Minaai M, Li S, Gaudino G, Pass HI, Carbone M, Yang H. HMGB1 as a therapeutic target in disease. J Cell Physiol 2020; 236:3406-3419. [PMID: 33107103 DOI: 10.1002/jcp.30125] [Citation(s) in RCA: 186] [Impact Index Per Article: 37.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2020] [Revised: 09/23/2020] [Accepted: 10/13/2020] [Indexed: 12/30/2022]
Abstract
High-mobility group box 1 (HMGB1) was initially recognized as a ubiquitous nuclear protein involved in maintaining the nucleosome integrity and facilitating gene transcription. HMGB1 has since been reevaluated to be a prototypical damage-associated molecular pattern (DAMP) protein, and together with its exogenous counterpart, pathogen-associated molecular pattern (PAMP), completes the body's alarmin system against disturbances in homeostasis. HMGB1 can be released into the extracellular matrix (ECM) by either granulocytes or necrotic cells to serve as a chemotaxis/cytokine during infection, endotoxemia, hypoxia, ischemia-reperfusion events, and cancer. Different isoforms of HMGB1 present with distinctive physiological functions in ECM-fully-reduced HMGB1 (all thiol) acts as the initial damage signal to recruit circulating myeloid cells, disulfide HMGB1 behaves as a cytokine to activate macrophages and neutrophils, and both signals are turned off when HMGB1 is terminally oxidized into the final sulfonate form. Targeting HMGB1 constitutes a favorable therapeutic strategy for inflammation and inflammatory diseases. Antagonists such as ethyl pyruvate inhibit HMGB1 by interfering with its cytoplasmic exportation, while others such as glycyrrhizin directly bind to HMGB1 and render it unavailable for its receptors. The fact that a mixture of different HMGB1 isoforms is present in the ECM poses a challenge in pinpointing the exact role of an individual antagonist. A more discriminative probe for HMGB1 may be necessary to advance our knowledge of HMGB1, HMGB1 antagonists, and inflammatory-related diseases.
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Affiliation(s)
- Jiaming Xue
- Thoracic Oncology Program, University of Hawaii Cancer Center, Honolulu, Hawaii, USA.,John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii, USA
| | - Joelle S Suarez
- Thoracic Oncology Program, University of Hawaii Cancer Center, Honolulu, Hawaii, USA
| | - Michael Minaai
- Thoracic Oncology Program, University of Hawaii Cancer Center, Honolulu, Hawaii, USA
| | - Shuangjing Li
- Thoracic Oncology Program, University of Hawaii Cancer Center, Honolulu, Hawaii, USA.,Central Laboratory of Liaocheng People's Hospital, Liaocheng, Shandong, China
| | - Giovanni Gaudino
- Thoracic Oncology Program, University of Hawaii Cancer Center, Honolulu, Hawaii, USA
| | - Harvey I Pass
- Department of Cardiothoracic Surgery, New York University Langone Medical Center, New York, New York, USA
| | - Michele Carbone
- Thoracic Oncology Program, University of Hawaii Cancer Center, Honolulu, Hawaii, USA
| | - Haining Yang
- Thoracic Oncology Program, University of Hawaii Cancer Center, Honolulu, Hawaii, USA
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30
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Chen L, Chi K, Xiang H, Yang Y. Circ_0032821 Facilitates Gastric Cancer Cell Proliferation, Migration, Invasion and Glycolysis by Regulating MiR-1236-3p/HMGB1 Axis. Cancer Manag Res 2020; 12:9965-9976. [PMID: 33116853 PMCID: PMC7567569 DOI: 10.2147/cmar.s270164] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Accepted: 09/10/2020] [Indexed: 01/03/2023] Open
Abstract
Background Circular RNAs (circRNAs) play an essential role in the pathogenesis of malignant tumors, including gastric cancer (GC). However, the effect of circ_0032821 on GC remains largely unknown. Methods QRT-PCR assay was employed to examine the levels of circ_0032821, CEP128 mRNA and miR-1236-3p. RNase R digestion assay was utilized to verify the feature of circ_0032821. Cell Counting Kit-8 (CCK-8) assay and transwell assay were adopted to evaluate cell proliferation and metastasis. The level of glycolysis was evaluated through detecting ECAR, OCR, lactate production, glucose uptake and ATP synthesis. Dual-luciferase reporter assay and RIP assay were conducted to analyze the relationship between miR-1236-3p and circ_0032821 or HMGB1. Western blot assay was adopted for high mobility group box 1 (HMGB1) level. Murine xenograft model assay was utilized for the effect of circ_0032821 in vivo. Results High level of circ_0032821 was observed in GC tissues and cells. Silencing of circ_0032821 markedly repressed cell proliferation, metastasis and glycolysis in GC cells in vitro and blocked tumorigenesis of GC in vivo. For mechanism analysis, circ_0032821 was identified as the sponge of miR-1236-3p and HMGB1 was the target gene of miR-1236-3p. Moreover, miR-1236-3p suppression restored the influences of circ_0032821 deficiency on GC cell proliferation, metastasis and glycolysis. Overexpression of miR-1236-3p relieved the malignant behaviors of GC cells by targeting HMGB1. Conclusion Circ_0032821 accelerated GC development through elevating HMGB1 expression via sponging miR-1236-3p.
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Affiliation(s)
- Lei Chen
- Department of Emergency Medicine, Xiang'an Hospital of Xiamen University, Xiamen, 361101, People's Republic of China
| | - Kun Chi
- Department of Nursing, Qingdao Municipal Hospital (Group), Qingdao 266071, People's Republic of China
| | - Huaguo Xiang
- Medical Laboratory, Shenzhen Baoan District Fuyong People's Hospital, Shenzhen 518103, People's Republic of China
| | - Yan Yang
- Department of Gastroenterology, Central People's Hospital of Tengzhou, Tengzhou 277500, People's Republic of China
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31
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Li L, Lv G, Wang B, Ma H. Long Noncoding RNA LINC00525 Promotes the Aggressive Phenotype of Chordoma Through Acting as a microRNA-505-3p Sponge and Consequently Raising HMGB1 Expression. Onco Targets Ther 2020; 13:9015-9027. [PMID: 32982292 PMCID: PMC7490091 DOI: 10.2147/ott.s268678] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2020] [Accepted: 08/11/2020] [Indexed: 12/13/2022] Open
Abstract
Purposes Long intergenic non-protein coding RNA 525 (LINC00525), a long noncoding RNA, has been implicated in the carcinogenesis and progression of many human cancer types. However, the detailed roles of LINC00525 in chordoma and the underlying mechanisms are not fully understood. Here, we aimed to determine whether LINC00525 could modulate the oncogenicity of chordoma cells and to elucidate in detail the molecular events underlying these tumor-promoting activities. Methods Reverse-transcription quantitative polymerase chain reactions were performed to assess LINC00525 expression in chordoma. The effects of LINC00525 silencing on chordoma cell proliferation, apoptosis, migration, and invasiveness in vitro and tumor growth in vivo were respectively tested using CCK-8 assay, flow cytometry, migration and invasion assays, and xenograft experiments. Results High LINC00525 expression levels were detected in chordoma tissues. The proliferative, migratory, and invasive abilities of chordoma cells in vitro and their tumor growth in vivo were suppressed by the LINC00525 knockdown, whereas apoptosis was induced by it. Mechanistically, LINC00525 acted as a molecular sponge of microRNA-505-3p (miR-505-3p) and upregulated the expression of high mobility group box 1 (HMGB1), which is directly targeted by miR-505-3p. Rescue assays indicated that increasing the output of miR-505-3p-HMGB1 axis attenuated the effects of LINC00525 depletion on chordoma cells. Conclusion LINC00525, a pro-oncogenic long noncoding RNA, promotes chordoma progression by regulating the miR-505-3p-HMGB1 axis. The LINC00525-miR-505-3p-HMGB1 pathway may be a novel therapeutic target in chordoma.
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Affiliation(s)
- Lei Li
- Department of Spine Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, People's Republic of China
| | - Guohua Lv
- Department of Spine Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, People's Republic of China
| | - Bing Wang
- Department of Spine Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, People's Republic of China
| | - Hong Ma
- Department of Spine Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, People's Republic of China
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Gao Y, Xu H, Pu T. MicroRNA-1179 suppresses the proliferation and enhances vincristine sensitivity of oral cancer cells via induction of apoptosis and modulation of MEK/ERK and PI3K/AKT signalling pathways. AMB Express 2020; 10:149. [PMID: 32809144 PMCID: PMC7434990 DOI: 10.1186/s13568-020-01082-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2020] [Accepted: 08/08/2020] [Indexed: 12/20/2022] Open
Abstract
The role of miR-1179 in the development of cancer has been proved by different studies. However, the expression profile and role of miR-1179 is yet to be explored in human oral cancer. Consistently, this study was undertaken to explore the molecular role of miR-1179 in regulation of the human oral cancer development and progression. The results showed miR-1179 to be significantly (p < 0.05) overexpressed in all the oral cancer cell lines relative to normal cells. The repression of miR-1179 transcript levels not only suppressed the proliferation of oral cancer cells but also increased their sensitivity to vincristine. The decline in proliferative rates was attributed to induction of autophagy in oral cancer cells as confirmed by transmission electron microscopic analysis. Western blot analysis showed that the expression of LC3B-II increased and that of beclin 1 decreased while LC3B-I expression remained constant upon miR-1179 inhibition. Inhibition of miR-1179 caused significant decrease in the migration and invasion of the oral cancer cells. The migration and invasion found to be 47% and 32% for SCC-9 and 24% and 28% for SCC-25 cells upon miR-1179 inhibition. At molecular level, the miR-1179 was shown to exert its anticancer effects via deactivation of MEK/ERK and PI3K/AKT signalling cascades. In conclusion, the findings point towards the potential of miR-1179 in the treatment of oral cancer.
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Yang S, Jiang Y, Ren X, Feng D, Zhang L, He D, Hong S, Jin L, Zhang F, Lu S. FOXA1-induced circOSBPL10 potentiates cervical cancer cell proliferation and migration through miR-1179/UBE2Q1 axis. Cancer Cell Int 2020; 20:389. [PMID: 32831649 PMCID: PMC7422615 DOI: 10.1186/s12935-020-01360-2] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2019] [Accepted: 06/17/2020] [Indexed: 01/30/2023] Open
Abstract
Background Recently, extensive evidence has clarified the crucial role of circular RNAs (circRNAs) as a pro-tumor or anti-cancer participant in human malignancies. A new circRNA derived from oxysterol binding protein like 10 (OSBPL10) (circOSBPL10) has not been researched in cervical cancer (CC) yet. Methods The expression of molecules was analyzed by RT-qPCR or western blot. Several functional assays were applied to explore the biological influence of circOSBPL10 on CC. The interaction between RNAs was estimated via luciferase reporter, RNA immunoprecipitation and RNA pull-down assays. Results CircOSBPL10 characterized with cyclic structure was revealed to possess elevated expression in CC cells. CircOSBPL10 downregulation elicited suppressive impacts on CC cell proliferation and migration. Interestingly, circOSBPL10 regulated CC progression by interacting with microRNA-1179 (miR-1179). Moreover, ubiquitin conjugating enzyme E2 Q1 (UBE2Q1) targeted by miR-1179 was positively regulated by circOSBPL10 in CC. Furthermore, enhanced UBE2Q1 expression or suppressed miR-1179 level countervailed the repressive effect of circOSBPL10 depletion on the malignant phenotypes of CC cells. Moreover, forkhead box A1 (FOXA1) was confirmed to induce circOSBPL10 expression in CC cells. Conclusions FOXA1-induced circOSBPL10 facilitates CC progression through miR-1179/UBE2Q1 axis, highlighting a strong potential for circOSBPL10 to serve as a promising therapeutic target in CC.
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Affiliation(s)
- Shanshan Yang
- Department of Gynecological Radiotherapy, Harbin Medical University Cancer Hospital, No. 150 Haping Road, Nangang District, Harbin, 150081 Heilongjiang China
| | - Yiwen Jiang
- Department of Radiotherapy, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, No. 55 Renmin South Road, Chengdu, 610041 Sichuan China
| | - Xiaoli Ren
- Department of Radiotherapy, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, No. 55 Renmin South Road, Chengdu, 610041 Sichuan China
| | - Dan Feng
- Department of Radiotherapy, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, No. 55 Renmin South Road, Chengdu, 610041 Sichuan China
| | - Liaoyun Zhang
- Department of Radiotherapy, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, No. 55 Renmin South Road, Chengdu, 610041 Sichuan China.,Pharmacy Department, Sichuan Jinxin Women and Children's Hospital, No. 66 Jingxiu Road, Jinjiang District, Chengdu, 610061 Sichuan China
| | - Deying He
- Department of Radiotherapy, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, No. 55 Renmin South Road, Chengdu, 610041 Sichuan China
| | - Shiyao Hong
- Department of Radiotherapy, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, No. 55 Renmin South Road, Chengdu, 610041 Sichuan China
| | - Li Jin
- Department of Radiotherapy, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, No. 55 Renmin South Road, Chengdu, 610041 Sichuan China
| | - Fang Zhang
- Department of Radiotherapy, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, No. 55 Renmin South Road, Chengdu, 610041 Sichuan China
| | - Shun Lu
- Department of Radiotherapy, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, No. 55 Renmin South Road, Chengdu, 610041 Sichuan China
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Qu X, Zhu L, Song L, Liu S. circ_0084927 promotes cervical carcinogenesis by sponging miR-1179 that suppresses CDK2, a cell cycle-related gene. Cancer Cell Int 2020; 20:333. [PMID: 32699532 PMCID: PMC7372805 DOI: 10.1186/s12935-020-01417-2] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2020] [Accepted: 07/13/2020] [Indexed: 12/13/2022] Open
Abstract
Background Cervical cancer (CC) is a malignant tumor found in the lowermost part of the womb. Evolving studies on CC have reported that circRNA plays a crucial role in CC progression. In this study, we investigated the main function of a novel circRNA, circ_0084927, and its regulatory network in CC development. Methods qRT-PCR was applied to evaluate the expression of circ_0084927, miR-1179, and CDK2 mRNA in CC tissues and cells. Dual-luciferase reporting experiments and RNA immunoprecipitation (RIP) assay were conducted to validate the target relationship of miR-1179 with circ_0084927 and CDK2 mRNA. CCK-8 and BrdU assays were also used to evaluate CC cell proliferation. The adhesion and apoptosis phenotypes of CC cells were measured using cell–matrix adhesion and caspase 3 activation assay. Flow cytometry was also employed to detect the CC cell cycle. Results Our results indicated that circ_0084927 was up-regulated in CC tissues and cells. Findings also revealed that circ_0084927 silence inhibited CC cell proliferation and adhesion while facilitating apoptosis and triggering cell cycle arrest. However, miR-1179 down-regulation appeared in CC tissues. Apart from observing that circ_0084927 abolished miR-1179’s inhibitory effects on cell proliferation and adhesion, it was found that CDK2 was up-regulated in CC tissues and was instrumental in cancer promotion. Also observed was that miR-1179 directly targeted CDK2, thereby inhibiting CDK2’s promotion on the malignant phenotypes of CC cells. Lastly, results indicated that circ_0084927 revoked the inhibitory effect of miR-1179 on CDK2 by sponging miR-1179. Conclusion circ_0084927 promoted cervical carcinogenesis by sequestering miR-1179, which directly targeted CDK2. Our results also provided novel candidate targets for CC treatment in that it revealed the circ_0084927/miR-1179/CDK2 regulatory network that strengthened CC aggressiveness.
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Affiliation(s)
- Xinhua Qu
- Department of Obstetrics, Yantai Affiliated Hospital, Binzhou Medical College, No. 717 Jinbu Street, Muping District, Yantai, 264100 Shandong China
| | - Liumei Zhu
- Department of Maternal and Child Health Promotion, Yantai Affiliated Hospital, Binzhou Medical College, No. 717 Jinbu Street, Muping District, Yantai, 264100 Shandong China
| | - Linlin Song
- Department of Obstetrics, Yantai Affiliated Hospital, Binzhou Medical College, No. 717 Jinbu Street, Muping District, Yantai, 264100 Shandong China
| | - Shaohua Liu
- Department of Obstetrics, Yantai Affiliated Hospital, Binzhou Medical College, No. 717 Jinbu Street, Muping District, Yantai, 264100 Shandong China
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Gao ZY, Liu H, Zhang Z. miR-144-3p increases radiosensibility of gastric cancer cells by targeting inhibition of ZEB1. Clin Transl Oncol 2020; 23:491-500. [PMID: 32613412 DOI: 10.1007/s12094-020-02436-1] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2020] [Accepted: 06/19/2020] [Indexed: 11/29/2022]
Abstract
PURPOSE This study set out to probe into the effect and mechanism of miR-144-3p on radiosensitivity of gastric cancer (GC) cells. METHODS Cancer tissue and paracancerous tissue of GC patients admitted to our hospital were collected, their miR-144-3p expression was tested, GC cells were transfected, and survival and biological behavior of those cells under radiation were detected. RESULTS After detection, miR-144-3p expression was down-regulated in GC tissue, while ZEB1 was up-regulated. There was no remarkable difference in the survival fraction of cells in each group before receiving radiation, but that of tumor cells decreased obviously (p < 0.05) after radiation exposure. Survival fraction of cells overexpressing miR-144-3p or silencing ZEB1 decreased more obviously, while the inhibition of miR-144-3p or overexpressing ZEB1 was weaker. Biological behavior of cells under 6 Gy radiation was detected. It was found that miR-144-3p overexpression or silencing ZEB1 dramatically inhibited the proliferation activity of GC cells under 6 Gy radiation, increased the levels of pro-apoptotic Bax and caspase-3 proteins (p < 0.05) and decreased the anti-apoptotic protein Bcl-2 level (p < 0.05), resulting in an increase in the apoptosis rate of cells. miR-144-3p was confirmed to be ZEB1 targeting site by dual luciferase report. Moreover, rescue experiments prove that it can increase the radiosensitivity of GC cells by regulating ZEB1 expression. CONCLUSION miR-144-3p expression was down-regulated in GC, and it can increase the radiosensitivity of those cells by inhibiting ZEB1 expression.
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Affiliation(s)
- Z Y Gao
- Department of Radiotherapy, Binzhou Central Hospital, No. 108 Huancheng Nan Road, Huimin County, Binzhou, 251700, Shandong, China.
| | - H Liu
- Department of Oncology, Binzhou Central Hospital, Ward 3, Binzhou, 251700, China
| | - Z Zhang
- Department of Radiotherapy, Binzhou Central Hospital, No. 108 Huancheng Nan Road, Huimin County, Binzhou, 251700, Shandong, China
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Tao Y, Zhao Y, Peng Y, Ma X, Sun C, Xu K. MicroRNA-621 inhibits the growth of gastric cancer cells by targeting SYF2. Arch Biochem Biophys 2020; 688:108406. [DOI: 10.1016/j.abb.2020.108406] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2020] [Revised: 05/05/2020] [Accepted: 05/06/2020] [Indexed: 02/07/2023]
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