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Zhang L, Zhang J, Zhang X, Liu S, Qi C, Gao S. miR‑100: A key tumor suppressor regulatory factor in human malignant tumors (Review). Int J Mol Med 2025; 55:67. [PMID: 40017111 PMCID: PMC11875724 DOI: 10.3892/ijmm.2025.5508] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2024] [Accepted: 01/02/2025] [Indexed: 03/01/2025] Open
Abstract
MicroRNA (miRNA/miR)‑100 is a crucial tumor‑suppressive miRNA that serves a pivotal role in the initiation and progression of various malignancies. miR‑100 regulates cancer cell proliferation, migration, invasion and apoptosis by targeting oncogenes, and acts as a molecular sponge to regulate long non‑coding RNAs and circular RNAs, thereby influencing processes such as glycolysis, autophagy and resistance to chemotherapy/radiotherapy. Furthermore, miR‑100 suppresses tumor progression by modulating key signaling pathways, including the PI3K/AKT and Wnt/β‑catenin signaling pathways. miR‑100 exhibits potential for early cancer diagnosis, particularly in cancer types such as gastric and lung cancer, where it can serve as a non‑invasive biomarker for early screening. As a therapeutic target, restoring miR‑100 expression can enhance the efficacy of chemotherapy or targeted therapy, thereby improving patient prognosis. Although challenges remain in its clinical application, including delivery systems and safety concerns, ongoing research suggests that miR‑100 holds promise for personalized treatment and early diagnosis. Given that cancer remains a global health challenge, research on miR‑100 provides hope for cancer therapy, particularly in China, where the mortality rates of malignancies such as gastric, lung and liver cancer continue to rise, further emphasizing its potential for clinical translation.
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Affiliation(s)
- Liang Zhang
- Department of General Surgery I, The First Affiliated Hospital of Jiamusi University, Jiamusi, Heilongjiang 154002, P.R. China
| | - Jiuling Zhang
- Department of General Surgery I, The First Affiliated Hospital of Jiamusi University, Jiamusi, Heilongjiang 154002, P.R. China
| | - Xue Zhang
- School of Basic Medical Sciences, Jiamusi University, Jiamusi, Heilongjiang 154002, P.R. China
| | - Shuang Liu
- School of Basic Medical Sciences, Jiamusi University, Jiamusi, Heilongjiang 154002, P.R. China
| | - Chunyu Qi
- School of Basic Medical Sciences, Jiamusi University, Jiamusi, Heilongjiang 154002, P.R. China
- Department of Infection, The First Affiliated Hospital of Jiamusi University, Jiamusi, Heilongjiang 154002, P.R. China
| | - Shengyu Gao
- Department of General Surgery I, The First Affiliated Hospital of Jiamusi University, Jiamusi, Heilongjiang 154002, P.R. China
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2
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Srisathaporn S, Ekalaksananan T, Heawchaiyaphum C, Aromseree S, Maranon DG, Altina NH, Nukpook T, Wilusz J, Pientong C. EBV-Induced LINC00944: A Driver of Oral Cancer Progression and Influencer of Macrophage Differentiation. Cancers (Basel) 2025; 17:491. [PMID: 39941858 PMCID: PMC11815735 DOI: 10.3390/cancers17030491] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2024] [Revised: 01/26/2025] [Accepted: 01/28/2025] [Indexed: 02/16/2025] Open
Abstract
Oral squamous cell carcinoma (OSCC) is a significant global health concern. Epstein-Barr virus (EBV) infection as well as long non-coding RNA (lncRNAs) associated EBV infection, have been linked to OSCC development and are known to influence cancer progression. LINC00944 is associated with various cancers and immune cells, but its role in oral cancer remains underexplored. This study investigated the role of EBV-induced LINC00944 in OSCC and its impact on the tumor microenvironment. The LINC00944 expression was analyzed from a database of head and neck squamous cell carcinoma (HNSCC) tissues, and its expression in EBV-positive and EBV-negative OSCC cell lines was examined via qRT-PCR. We overexpressed LINC00944 in SCC25 and ORL-48T oral cancer cell lines and evaluated its impact on migration and invasion ability using wound healing and transwell experiments. Additionally, we studied its influence on macrophage differentiation. The results showed that LINC00944 expression was higher in HNSCC than in normal tissues and was linked to EBV-positive OSCC cell lines. LINC00944 overexpressed-OSCC cell lines significantly increased cellular motility and invasiveness. Additionally, LINC00944 was secreted in a cultured medium, delivered to macrophages, and promoted macrophage differentiation into the M1 subtype. Predicted interactions suggested that LINC00944 targets miRNAs that regulate NFKB1 and RELA. In conclusion, EBV-induced LINC00944 contributes to OSCC progression by enhancing tumor cell migration, invasion, and macrophage differentiation, potentially regulating these processes through NFKB1 and RELA. These findings provide valuable directions for LINC00944's future studies on its mechanisms and suggest that it could be a target of study in EBV-associated OSCC.
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Affiliation(s)
- Sawarot Srisathaporn
- Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand; (S.S.); (T.E.); (C.H.); (S.A.); (T.N.)
- Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO 80523, USA; (D.G.M.); (N.H.A.)
- HPV & EBV and Carcinogenesis Research Group, Khon Kaen University, Khon Kaen 40002, Thailand
| | - Tipaya Ekalaksananan
- Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand; (S.S.); (T.E.); (C.H.); (S.A.); (T.N.)
- HPV & EBV and Carcinogenesis Research Group, Khon Kaen University, Khon Kaen 40002, Thailand
| | - Chukkris Heawchaiyaphum
- Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand; (S.S.); (T.E.); (C.H.); (S.A.); (T.N.)
- HPV & EBV and Carcinogenesis Research Group, Khon Kaen University, Khon Kaen 40002, Thailand
| | - Sirinart Aromseree
- Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand; (S.S.); (T.E.); (C.H.); (S.A.); (T.N.)
- HPV & EBV and Carcinogenesis Research Group, Khon Kaen University, Khon Kaen 40002, Thailand
| | - David G. Maranon
- Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO 80523, USA; (D.G.M.); (N.H.A.)
| | - Noelia H. Altina
- Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO 80523, USA; (D.G.M.); (N.H.A.)
| | - Thawaree Nukpook
- Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand; (S.S.); (T.E.); (C.H.); (S.A.); (T.N.)
- HPV & EBV and Carcinogenesis Research Group, Khon Kaen University, Khon Kaen 40002, Thailand
| | - Jeffrey Wilusz
- Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO 80523, USA; (D.G.M.); (N.H.A.)
| | - Chamsai Pientong
- Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand; (S.S.); (T.E.); (C.H.); (S.A.); (T.N.)
- HPV & EBV and Carcinogenesis Research Group, Khon Kaen University, Khon Kaen 40002, Thailand
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3
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Srisathaporn S, Pientong C, Heawchaiyaphum C, Nukpook T, Aromseree S, Ekalaksananan T. The Oncogenic Role of VWA8-AS1, a Long Non-Coding RNA, in Epstein-Barr Virus-Associated Oral Squamous Cell Carcinoma: An Integrative Transcriptome and Functional Analysis. Int J Mol Sci 2024; 25:12565. [PMID: 39684278 DOI: 10.3390/ijms252312565] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2024] [Revised: 11/16/2024] [Accepted: 11/21/2024] [Indexed: 12/18/2024] Open
Abstract
Dysregulated long non-coding RNA (lncRNA) expression is linked to various cancers and may be influenced by oncogenic Epstein-Barr virus (EBV) infection, a known and detectable risk factor in oral squamous cell carcinoma (OSCC) patients. However, research on the oncogenic role of EBV-induced lncRNAs in OSCC is limited. To identify lncRNA-associated EBV infection and OSCC carcinogenesis, the differential expression of RNA-seq datasets from paired normal adjacent and OSCC tissues, and microarray data from EBV-negative and EBV-positive SCC25 cells, were identified and selected, respectively, for interaction, functional analysis, and CCK-8 cell proliferation, wound healing, and invasion Transwell assays. In OSCC tissues, 6731 differentially expressed lncRNAs were identified when compared to normal tissues from RNA-seq datasets, with 295 linked to EBV-induced OSCC carcinogenesis from microarray datasets. The EBV-induced lncRNA VWA8-AS1 showed significant upregulation in EBV-positive SCC25 cells and EBV-infected adjacent and OSCC tissue samples. VWA8-AS1 potentially promotes OSCC via the lncRNA-miRNA-mRNA axis or direct protein interactions, affecting various cellular processes. Studies in OSCC cell lines revealed that elevated VWA8-AS1 levels enhanced cell migration and invasion. This study demonstrates VWA8-AS1's contribution to tumor progression and possible interactions with its targets in OSCC, offering insights for future research on functional mechanisms and therapeutic targets in EBV-associated OSCC.
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Affiliation(s)
- Sawarot Srisathaporn
- Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
- HPV & EBV and Carcinogenesis Research Group, Khon Kaen University, Khon Kaen 40002, Thailand
| | - Chamsai Pientong
- Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
- HPV & EBV and Carcinogenesis Research Group, Khon Kaen University, Khon Kaen 40002, Thailand
| | - Chukkris Heawchaiyaphum
- Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
- HPV & EBV and Carcinogenesis Research Group, Khon Kaen University, Khon Kaen 40002, Thailand
| | - Thawaree Nukpook
- Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
- HPV & EBV and Carcinogenesis Research Group, Khon Kaen University, Khon Kaen 40002, Thailand
| | - Sirinart Aromseree
- Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
- HPV & EBV and Carcinogenesis Research Group, Khon Kaen University, Khon Kaen 40002, Thailand
| | - Tipaya Ekalaksananan
- Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
- HPV & EBV and Carcinogenesis Research Group, Khon Kaen University, Khon Kaen 40002, Thailand
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4
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Umapathy VR, Natarajan PM, Swamikannu B. Molecular and Therapeutic Roles of Non-Coding RNAs in Oral Cancer-A Review. Molecules 2024; 29:2402. [PMID: 38792263 PMCID: PMC11123887 DOI: 10.3390/molecules29102402] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2024] [Revised: 05/09/2024] [Accepted: 05/12/2024] [Indexed: 05/26/2024] Open
Abstract
Oral cancer (OC) is among the most common malignancies in the world. Despite advances in therapy, the worst-case scenario for OC remains metastasis, with a 50% survival rate. Therefore, it is critical to comprehend the pathophysiology of the condition and to create diagnostic and treatment plans for OC. The development of high-throughput genome sequencing has revealed that over 90% of the human genome encodes non-coding transcripts, or transcripts that do not code for any proteins. This paper describes the function of these different kinds of non-coding RNAs (ncRNAs) in OC as well as their intriguing therapeutic potential. The onset and development of OC, as well as treatment resistance, are linked to dysregulated ncRNA expression. These ncRNAs' potentially significant roles in diagnosis and prognosis have been suggested by their differing expression in blood or saliva. We have outlined every promising feature of ncRNAs in the treatment of OC in this study.
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Affiliation(s)
- Vidhya Rekha Umapathy
- Department of Public Health Dentistry, Dr. M.G.R. Educational and Research Institute, Thai Moogambigai Dental College and Hospital, Chennai 600107, Tamil Nadu, India
| | - Prabhu Manickam Natarajan
- Department of Clinical Sciences, Centre of Medical and Bio-Allied Health Sciences and Research Ajman University, Ajman P.O. Box 346, United Arab Emirates
| | - Bhuminathan Swamikannu
- Department of Prosthodontics, Sree Balaji Dental College and Hospital, Pallikaranai, BIHER, Chennai 600100, Tamil Nadu, India;
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5
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Pruthi N, Yap T, Moore C, Cirillo N, McCullough MJ. Applying Machine Learning for Enhanced MicroRNA Analysis: A Companion Risk Tool for Oral Squamous Cell Carcinoma in Standard Care Incisional Biopsy. Biomolecules 2024; 14:458. [PMID: 38672474 PMCID: PMC11048287 DOI: 10.3390/biom14040458] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2024] [Revised: 04/04/2024] [Accepted: 04/06/2024] [Indexed: 04/28/2024] Open
Abstract
Machine learning analyses within the realm of oral cancer outcomes are relatively underexplored compared to other cancer types. This study aimed to assess the performance of machine learning algorithms in identifying oral cancer patients, utilizing microRNA expression data. In this study, we implemented this approach using a panel of oral cancer-associated microRNAs sourced from standard incisional biopsy specimens to identify cases of oral squamous cell carcinomas (OSCC). For the model development process, we used a dataset comprising 30 OSCC and 30 histologically normal epithelium (HNE) cases. We initially trained a logistic regression prediction model using 70 percent of the dataset, while reserving the remaining 30 percent for testing. Subsequently, the model underwent hyperparameter tuning resulting in enhanced performance metrics. The hyperparameter-tuned model exhibited high accuracy (0.894) and ROC AUC (0.898) in predicting OSCC. Testing the model on cases of potentially malignant disorders (OPMDs) revealed that leukoplakia with mild dysplasia was predicted as having a high risk of progressing to OSCC, emphasizing machine learning's advantage over histopathology in detecting early molecular changes. These findings underscore the necessity for further refinement, incorporating a broader set of variables to enhance the model's predictive capabilities in assessing the risk of oral potentially malignant disorders.
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Affiliation(s)
| | | | | | | | - Michael J. McCullough
- Melbourne Dental School, The University of Melbourne, Carlton, VIC 3053, Australia; (N.P.); (T.Y.); (C.M.); (N.C.)
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Tan H, Guo M, Chen J, Wang J, Yu G. HetFCM: functional co-module discovery by heterogeneous network co-clustering. Nucleic Acids Res 2024; 52:e16. [PMID: 38088228 PMCID: PMC10853805 DOI: 10.1093/nar/gkad1174] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2023] [Revised: 10/31/2023] [Accepted: 11/23/2023] [Indexed: 02/10/2024] Open
Abstract
Functional molecular module (i.e., gene-miRNA co-modules and gene-miRNA-lncRNA triple-layer modules) analysis can dissect complex regulations underlying etiology or phenotypes. However, current module detection methods lack an appropriate usage and effective model of multi-omics data and cross-layer regulations of heterogeneous molecules, causing the loss of critical genetic information and corrupting the detection performance. In this study, we propose a heterogeneous network co-clustering framework (HetFCM) to detect functional co-modules. HetFCM introduces an attributed heterogeneous network to jointly model interplays and multi-type attributes of different molecules, and applies multiple variational graph autoencoders on the network to generate cross-layer association matrices, then it performs adaptive weighted co-clustering on association matrices and attribute data to identify co-modules of heterogeneous molecules. Empirical study on Human and Maize datasets reveals that HetFCM can find out co-modules characterized with denser topology and more significant functions, which are associated with human breast cancer (subtypes) and maize phenotypes (i.e., lipid storage, drought tolerance and oil content). HetFCM is a useful tool to detect co-modules and can be applied to multi-layer functional modules, yielding novel insights for analyzing molecular mechanisms. We also developed a user-friendly module detection and analysis tool and shared it at http://www.sdu-idea.cn/FMDTool.
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Affiliation(s)
- Haojiang Tan
- School of Software, Shandong University, Jinan 250101, Shandong, China
- Joint SDU-NTU Centre for Artificial Intelligence Research, Shandong University, Jinan 250101, Shandong, China
| | - Maozu Guo
- College of Electrical and Information Engineering, Beijing Uni. of Civil Eng. and Arch., Beijing 100044, China
| | - Jian Chen
- College of Agronomy & Biotechnolog, China Agricultural University, Beijing 100193, China
| | - Jun Wang
- Joint SDU-NTU Centre for Artificial Intelligence Research, Shandong University, Jinan 250101, Shandong, China
| | - Guoxian Yu
- School of Software, Shandong University, Jinan 250101, Shandong, China
- Joint SDU-NTU Centre for Artificial Intelligence Research, Shandong University, Jinan 250101, Shandong, China
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7
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Doghish AS, Elshaer SS, Fathi D, Rizk NI, Elrebehy MA, Al-Noshokaty TM, Elballal MS, Abdelmaksoud NM, Abdel-Reheim MA, Abdel Mageed SS, Zaki MB, Mohammed OA, Tabaa MME, Elballal AS, Saber S, El-Husseiny HM, Abulsoud AI. Unraveling the role of miRNAs in the diagnosis, progression, and drug resistance of oral cancer. Pathol Res Pract 2024; 253:155027. [PMID: 38101159 DOI: 10.1016/j.prp.2023.155027] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2023] [Revised: 12/06/2023] [Accepted: 12/07/2023] [Indexed: 12/17/2023]
Abstract
Oral cancer (OC) is a widely observed neoplasm on a global scale. Over time, there has been an increase in both its fatality and incidence rates. Oral cancer metastasis is a complex process that involves a number of cellular mechanisms, including invasion, migration, proliferation, and escaping from malignant tissue through either lymphatic or vascular channels. MicroRNAs (miRNAs) are a crucial class of short non-coding RNAs recognized as significant modulators of diverse cellular processes and exert a pivotal influence on the carcinogenesis pathway, functioning either as tumor suppressors or as oncogenes. It has been shown that microRNAs (miRNAs) have a role in metastasis at several stages, including epithelial-mesenchymal transition, migration, invasion, and colonization. This regulation is achieved by targeting key genes involved in these pathways by miRNAs. This paper aims to give a contemporary analysis of OC, focusing on its molecular genetics. The current literature and emerging advancements in miRNA dysregulation in OC are thoroughly examined. This project would advance OC diagnosis, prognosis, therapy, and therapeutic implications.
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Affiliation(s)
- Ahmed S Doghish
- Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt; Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City 11231, Cairo, Egypt.
| | - Shereen Saeid Elshaer
- Biochemistry Department, Faculty of Pharmacy, Heliopolis University, Cairo 11785, Egypt; Department of Biochemistry, Faculty of Pharmacy (Girls), Al-Azhar University, Nasr city, Cairo 11823, Egypt
| | - Doaa Fathi
- Biochemistry Department, Faculty of Pharmacy, Heliopolis University, Cairo 11785, Egypt
| | - Nehal I Rizk
- Biochemistry Department, Faculty of Pharmacy, Heliopolis University, Cairo 11785, Egypt
| | - Mahmoud A Elrebehy
- Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt
| | - Tohada M Al-Noshokaty
- Biochemistry Department, Faculty of Pharmacy, Heliopolis University, Cairo 11785, Egypt
| | - Mohammed S Elballal
- Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt
| | | | - Mustafa Ahmed Abdel-Reheim
- Department of Pharmaceutical Sciences, College of Pharmacy, Shaqra University, Shaqra 11961, Saudi Arabia; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Beni-Suef University, Beni, Suef 62521, Egypt.
| | - Sherif S Abdel Mageed
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt
| | - Mohamed Bakr Zaki
- Department of Biochemistry, Faculty of Pharmacy, University of Sadat City, Menoufia 32897, Egypt
| | - Osama A Mohammed
- Department of Pharmacology, College of Medicine, University of Bisha, Bisha 61922, Saudi Arabia
| | - Manar Mohammed El Tabaa
- Pharmacology & Environmental Toxicology, Environmental Studies & Research Institute (ESRI), University of Sadat City, Sadat City 32897, Menoufia, Egypt
| | - Ahmed S Elballal
- Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Cairo University, Egypt
| | - Sameh Saber
- Department of Pharmacology, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa 11152, Egypt
| | - Hussein M El-Husseiny
- Laboratory of Veterinary Surgery, Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai Cho, Fuchu-shi, Tokyo 183-8509, Japan; Department of Surgery, Anesthesiology, and Radiology, Faculty of Veterinary Medicine, Benha University, Moshtohor, Toukh, Elqaliobiya 13736, Egypt
| | - Ahmed I Abulsoud
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City 11231, Cairo, Egypt; Biochemistry Department, Faculty of Pharmacy, Heliopolis University, Cairo 11785, Egypt.
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8
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Doghish AS, El-Husseiny AA, Khidr EG, Elrebehy MA, Elballal MS, Abdel-Reheim MA, Abdel Mageed SS, Zaki MB, Mohammed OA, Khaled R, El-Dakroury WA, Noureldin S, Moustafa YM, Mangoura SA, Gedawy EM, Abulsoud AI. Decoding the role of miRNAs in oral cancer pathogenesis: A focus on signaling pathways. Pathol Res Pract 2023; 252:154949. [PMID: 37992507 DOI: 10.1016/j.prp.2023.154949] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2023] [Revised: 11/07/2023] [Accepted: 11/12/2023] [Indexed: 11/24/2023]
Abstract
Oral cancer (OC) is the predominant type originating in the head and neck region. The incidence of OC is mostly associated with behavioral risk factors, including tobacco smoking and excessive alcohol intake. Additionally, there is a lower but still significant association with viral infections such as human papillomaviruses and Epstein-Barr viruses. Furthermore, it has been observed that heritable genetic variables are linked to the risk of OC, in addition to the previously mentioned acquired risk factors. The current absence of biomarkers for OC diagnosis contributes to the frequent occurrence of advanced-stage diagnoses among patients. Non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs, and circular RNAs, have been observed to exert a significant effect on the transcriptional control of target genes involved in cancer, either through direct or indirect mechanisms. miRNAs are a class of short ncRNAs that play a role in regulating gene expression by enabling mRNA degradation or translational repression at the post-transcriptional phase. miRNAs are known to play a fundamental role in the development of cancer and the regulation of oncogenic cell processes. Notch signaling, PTEN/Akt/mTOR axis, KRAS mutation, JAK/STAT signaling, P53, EGFR, and the VEGFs have all been linked to OC, and miRNAs have been shown to have a role in all of these. The dysregulation of miRNA has been identified in cases of OC and is linked with prognosis.
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Affiliation(s)
- Ahmed S Doghish
- Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr, Cairo 11829, Egypt; Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr, Cairo 11231, Egypt.
| | - Ahmed A El-Husseiny
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr, Cairo 11231, Egypt; Department of Biochemistry, Faculty of Pharmacy, Egyptian Russian University, Badr, Cairo 11829, Egypt
| | - Emad Gamil Khidr
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr, Cairo 11231, Egypt
| | - Mahmoud A Elrebehy
- Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr, Cairo 11829, Egypt
| | - Mohammed S Elballal
- Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr, Cairo 11829, Egypt
| | - Mustafa Ahmed Abdel-Reheim
- Department of Pharmaceutical Sciences, College of Pharmacy, Shaqra University, Shaqra 11961, Saudi Arabia; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Beni-Suef University, Beni Suef 62521, Egypt.
| | - Sherif S Abdel Mageed
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr, Cairo 11829, Egypt
| | - Mohamed Bakr Zaki
- Biochemistry, Department of Biochemistry, Faculty of Pharmacy, University of Sadat City, Menoufia 32897, Egypt
| | - Osama A Mohammed
- Department of Pharmacology, College of Medicine, University of Bisha, Bisha 61922, Saudi Arabia.
| | - Reem Khaled
- Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr, Cairo 11829, Egypt
| | - Walaa A El-Dakroury
- Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr, Cairo 11829, Egypt
| | - Salma Noureldin
- Faculty of Dentistry, Badr University in Cairo (BUC), Badr, Cairo 11829, Egypt
| | - Yasser M Moustafa
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr, Cairo 11829, Egypt
| | - Safwat Abdelhady Mangoura
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr, Cairo 11829, Egypt
| | - Ehab M Gedawy
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Pharmaceutical Industries, Badr University in Cairo (BUC), Badr, P.O. Box 11829, Cairo, Egypt
| | - Ahmed I Abulsoud
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr, Cairo 11231, Egypt; Biochemistry Department, Faculty of Pharmacy, Heliopolis University, Cairo 11785, Egypt
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9
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Kozłowska-Masłoń J, Guglas K, Kolenda T, Lamperska K, Makałowska I. miRNA in head and neck squamous cell carcinomas: promising but still distant future of personalized oncology. Rep Pract Oncol Radiother 2023; 28:681-697. [PMID: 38179293 PMCID: PMC10764040 DOI: 10.5603/rpor.96666] [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: 02/27/2023] [Accepted: 07/24/2023] [Indexed: 01/06/2024] Open
Abstract
Head and neck squamous cell carcinoma is one of the most common and fatal cancers worldwide. Lack of appropriate preventive screening tests, late detection, and high heterogeneity of these tumors are the main reasons for the unsatisfactory effects of therapy and, consequently, unfavorable outcomes for patients. An opportunity to improve the quality of diagnostics and treatment of this group of cancers are microRNAs (miRNAs) - molecules with a great potential both as biomarkers and therapeutic targets. This review aims to present the characteristics of these short non-coding RNAs (ncRNAs) and summarize the current reports on their use in oncology focused on medical strategies tailored to patients' needs.
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Affiliation(s)
- Joanna Kozłowska-Masłoń
- Laboratory of Cancer Genetics, Greater oland Cancer Centre, Poznan, Poland
- Institute of Human Biology and Evolution, Faculty of Biology, Adam Mickiewicz University, Poznan, Poland
| | - Kacper Guglas
- Laboratory of Cancer Genetics, Greater oland Cancer Centre, Poznan, Poland
- Postgraduate School of Molecular Medicine, Medical University of Warsaw, Warsaw, Poland
| | - Tomasz Kolenda
- Laboratory of Cancer Genetics, Greater oland Cancer Centre, Poznan, Poland
- Research and Implementation Unit, Greater Poland Cancer Centre, Poznan, Poland
| | - Katarzyna Lamperska
- Laboratory of Cancer Genetics, Greater oland Cancer Centre, Poznan, Poland
- Research and Implementation Unit, Greater Poland Cancer Centre, Poznan, Poland
| | - Izabela Makałowska
- Institute of Human Biology and Evolution, Faculty of Biology, Adam Mickiewicz University, Poznan, Poland
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10
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Dey S, Biswas B, Manoj Appadan A, Shah J, Pal JK, Basu S, Sur S. Non-Coding RNAs in Oral Cancer: Emerging Roles and Clinical Applications. Cancers (Basel) 2023; 15:3752. [PMID: 37568568 PMCID: PMC10417002 DOI: 10.3390/cancers15153752] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2023] [Revised: 06/29/2023] [Accepted: 07/12/2023] [Indexed: 08/13/2023] Open
Abstract
Oral cancer (OC) is among the most prevalent cancers in the world. Certain geographical areas are disproportionately affected by OC cases due to the regional differences in dietary habits, tobacco and alcohol consumption. However, conventional therapeutic methods do not yield satisfying treatment outcomes. Thus, there is an urgent need to understand the disease process and to develop diagnostic and therapeutic strategies for OC. In this review, we discuss the role of various types of ncRNAs in OC, and their promising clinical implications as prognostic or diagnostic markers and therapeutic targets. MicroRNA (miRNA), long ncRNA (lncRNA), circular RNA (circRNA), PIWI-interacting RNA (piRNA), and small nucleolar RNA (snoRNA) are the major ncRNA types whose involvement in OC are emerging. Dysregulated expression of ncRNAs, particularly miRNAs, lncRNAs, and circRNAs, are linked with the initiation, progression, as well as therapy resistance of OC via modulation in a series of cellular pathways through epigenetic, transcriptional, post-transcriptional, and translational modifications. Differential expressions of miRNAs and lncRNAs in blood, saliva or extracellular vesicles have indicated potential diagnostic and prognostic importance. In this review, we have summarized all the promising aspects of ncRNAs in the management of OC.
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Affiliation(s)
| | | | | | | | | | - Soumya Basu
- Cancer and Translational Research Centre, Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth (DPU), Pimpri 411033, India; (S.D.)
| | - Subhayan Sur
- Cancer and Translational Research Centre, Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth (DPU), Pimpri 411033, India; (S.D.)
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11
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The paradigm of miRNA and siRNA influence in Oral-biome. Biomed Pharmacother 2023; 159:114269. [PMID: 36682246 DOI: 10.1016/j.biopha.2023.114269] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2022] [Revised: 01/12/2023] [Accepted: 01/16/2023] [Indexed: 01/22/2023] Open
Abstract
Short nucleotide sequences like miRNA and siRNA have attracted a lot of interest in Oral-biome investigations. miRNA is a small class of non-coding RNA that regulates gene expression to provide effective regulation of post-transcription. On contrary, siRNA is 21-25 nucleotide dsRNA impairing gene function post-transcriptionally through inhibition of mRNA for homologous dependent gene silencing. This review highlights the application of miRNA in oral biome including oral cancer, dental implants, periodontal diseases, gingival fibroblasts, oral submucous fibrosis, radiation-induced oral mucositis, dental Pulp, and oral lichenoid disease. Moreover, we have also discussed the application of siRNA against the aforementioned disease along with the impact of miRNA and siRNA to the various pathways and molecular effectors pertaining to the dental diseases. The influence of upregulation and downregulation of molecular effector post-treatment with miRNA and siRNA and their impact on the clinical setting has been elucidated. Thus, the mentioned details on application of miRNA and siRNA will provide a novel gateway to the scholars to not only mitigate the long-lasting issue in dentistry but also develop new theragnostic approaches.
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12
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Thomaidou AC, Batsaki P, Adamaki M, Goulielmaki M, Baxevanis CN, Zoumpourlis V, Fortis SP. Promising Biomarkers in Head and Neck Cancer: The Most Clinically Important miRNAs. Int J Mol Sci 2022; 23:ijms23158257. [PMID: 35897831 PMCID: PMC9367895 DOI: 10.3390/ijms23158257] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2022] [Revised: 07/18/2022] [Accepted: 07/21/2022] [Indexed: 02/01/2023] Open
Abstract
Head and neck cancers (HNCs) comprise a heterogeneous group of tumors that extend from the oral cavity to the upper gastrointestinal tract. The principal etiologic factors for oral tumors include tobacco smoking and alcohol consumption, while human papillomavirus (HPV) infections have been accused of a high incidence of pharyngeal tumors. Accordingly, HPV detection has been extensively used to categorize carcinomas of the head and neck. The diverse nature of HNC highlights the necessity for novel, sensitive, and precise biomarkers for the prompt diagnosis of the disease, its successful monitoring, and the timely prognosis of patient clinical outcomes. In this context, the identification of certain microRNAs (miRNAs) and/or the detection of alterations in their expression patterns, in a variety of somatic fluids and tissues, could serve as valuable biomarkers for precision oncology. In the present review, we summarize some of the most frequently studied miRNAs (including miR-21, -375, -99, -34a, -200, -31, -125a/b, -196a/b, -9, -181a, -155, -146a, -23a, -16, -29, and let-7), their role as biomarkers, and their implication in HNC pathogenesis. Moreover, we designate the potential of given miRNAs and miRNA signatures as novel diagnostic and prognostic tools for successful patient stratification. Finally, we discuss the currently ongoing clinical trials that aim to identify the diagnostic, prognostic, or therapeutic utility of miRNAs in HNC.
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Affiliation(s)
- Arsinoe C. Thomaidou
- Biomedical Applications Unit, Institute of Chemical Biology, National Hellenic Research Foundation (NHRF), 11635 Athens, Greece; (A.C.T.); (M.A.)
| | - Panagiota Batsaki
- Cancer Immunology and Immunotherapy Center, Saint Savas Cancer Hospital, 11522 Athens, Greece; (P.B.); (M.G.); (C.N.B.)
| | - Maria Adamaki
- Biomedical Applications Unit, Institute of Chemical Biology, National Hellenic Research Foundation (NHRF), 11635 Athens, Greece; (A.C.T.); (M.A.)
| | - Maria Goulielmaki
- Cancer Immunology and Immunotherapy Center, Saint Savas Cancer Hospital, 11522 Athens, Greece; (P.B.); (M.G.); (C.N.B.)
| | - Constantin N. Baxevanis
- Cancer Immunology and Immunotherapy Center, Saint Savas Cancer Hospital, 11522 Athens, Greece; (P.B.); (M.G.); (C.N.B.)
| | - Vassilis Zoumpourlis
- Biomedical Applications Unit, Institute of Chemical Biology, National Hellenic Research Foundation (NHRF), 11635 Athens, Greece; (A.C.T.); (M.A.)
- Correspondence: (V.Z.); (S.P.F.); Tel.: +30-210-727-3730 (V.Z.); +30-210-640-9462 (S.P.F.)
| | - Sotirios P. Fortis
- Cancer Immunology and Immunotherapy Center, Saint Savas Cancer Hospital, 11522 Athens, Greece; (P.B.); (M.G.); (C.N.B.)
- Correspondence: (V.Z.); (S.P.F.); Tel.: +30-210-727-3730 (V.Z.); +30-210-640-9462 (S.P.F.)
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13
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Yao T, Yao Y, Chen Z, Peng Y, Zhong G, Huang C, Li J, Li R. CircCASC15-miR-100-mTOR may influence the cervical cancer radioresistance. Cancer Cell Int 2022; 22:165. [PMID: 35477450 PMCID: PMC9044740 DOI: 10.1186/s12935-022-02573-3] [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: 11/06/2021] [Accepted: 04/06/2022] [Indexed: 11/20/2022] Open
Abstract
Background Cervical cancer has ranked the top one in gynecological malignancies for incidence. Radioresistance is now becoming a leading reason of recurrence. Methods Our microRNA array data indicated that the miRNA-100 level decreased significantly during radioresistance. In this study, we up-regulated miR-100 in Hela and Siha cells by using miR-100 mimics and observed proliferation and invasion. Results It turned out that with overexpression of miR-100, the cells had less invasiveness as well as proliferation. It may target gene mTOR, and it deed reduced EMT. To examine the role of miR-100 in radioresistance, there was no significant result showed by BSP. While the circCASC15 has been identified with sponge function according to RNA pull down and ISH. Conclusion The conclusions indicate miR-100 is a tumor suppressor gene and could be a therapeutic target in radio-resistant cervical cancers.
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Affiliation(s)
- Tingting Yao
- Department of Gynecological Oncology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yan Jiang West Road, Guangzhou, 510120, People's Republic of China. .,Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes, Sun Yat-Sen University, Guangzhou, China.
| | - Yao Yao
- Guangdong Food and Drug Vocational College, Guangzhou, China
| | - Zhiliao Chen
- Department of Gynecological Oncology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yan Jiang West Road, Guangzhou, 510120, People's Republic of China
| | - Yongpai Peng
- Department of Gynecological Oncology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yan Jiang West Road, Guangzhou, 510120, People's Republic of China
| | - Guanglei Zhong
- Department of Gynecological Oncology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yan Jiang West Road, Guangzhou, 510120, People's Republic of China
| | - Chunxian Huang
- Department of Gynecological Oncology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yan Jiang West Road, Guangzhou, 510120, People's Republic of China
| | - Jing Li
- Department of Gynecological Oncology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yan Jiang West Road, Guangzhou, 510120, People's Republic of China
| | - Ruixin Li
- Department of Gynecological Oncology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yan Jiang West Road, Guangzhou, 510120, People's Republic of China
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14
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Scholtz B, Horváth J, Tar I, Kiss C, Márton IJ. Salivary miR-31-5p, miR-345-3p, and miR-424-3p Are Reliable Biomarkers in Patients with Oral Squamous Cell Carcinoma. Pathogens 2022; 11:pathogens11020229. [PMID: 35215172 PMCID: PMC8876825 DOI: 10.3390/pathogens11020229] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2022] [Revised: 02/07/2022] [Accepted: 02/07/2022] [Indexed: 12/27/2022] Open
Abstract
If not detected early, oral squamous cell carcinoma (OSCC) has very poor prognosis, emphasizing the need for reliable early diagnostics. Saliva is considered a promising surrogate biosample for OSCC detection, because it comes into contact with many cells of the tumor mass, providing a comprehensive sampling of tumor-specific biomolecules. Although several protein- and RNA-based salivary biomarkers have been proposed for the detection of OSCC, the results of the studies show large differences. Our goal was to clarify which salivary microRNAs (miRNA) show reliably high expression in the saliva of OSCC patients, to be used as cancer-specific biomarkers, and potentially as early diagnostic biomarkers. Based on a detailed literature search, we selected six miRNAs commonly overexpressed in OSCC, and analyzed their expression in saliva samples of cancer patients and controls by real-time quantitative PCR. Our results suggest that miR-345 and miR-31-5p are consistently upregulated salivary biomarkers for OSCC, and a three-miRNA panel of miR-345, miR-31-5p, and miR-424-3p can distinguish cancer and control patients with high sensitivity.
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Affiliation(s)
- Beáta Scholtz
- Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary
- Correspondence: ; Tel.: +36-30-634-6065; Fax: +36-52-314-989
| | - József Horváth
- Doctoral School of Molecular Cell and Immune Biology, University of Debrecen, 4032 Debrecen, Hungary;
| | - Ildikó Tar
- Department of Oral Medicine, Faculty of Dentistry, University of Debrecen, 4032 Debrecen, Hungary;
| | - Csongor Kiss
- Department of Pediatrics, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary;
| | - Ildikó J. Márton
- Department of Restorative Dentistry, Faculty of Dentistry, University of Debrecen, 4032 Debrecen, Hungary;
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15
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Garnier D, Ratcliffe E, Briand J, Cartron PF, Oliver L, Vallette FM. The Activation of Mesenchymal Stem Cells by Glioblastoma Microvesicles Alters Their Exosomal Secretion of miR-100-5p, miR-9-5p and let-7d-5p. Biomedicines 2022; 10:biomedicines10010112. [PMID: 35052791 PMCID: PMC8773192 DOI: 10.3390/biomedicines10010112] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Revised: 12/28/2021] [Accepted: 12/31/2021] [Indexed: 02/01/2023] Open
Abstract
Glioblastoma (GBM) is the most aggressive brain tumor, and despite initial response to chemo- and radio-therapy, the persistence of glioblastoma stem cells (GSCs) unfortunately always results in tumor recurrence. It is now largely admitted that tumor cells recruit normal cells, including mesenchymal stem cells (MSCs), and components of their environment, to participate in tumor progression, building up what is called the tumor microenvironment (TME). While growth factors and cytokines constitute essential messengers to pass on signals between tumor and TME, recent uncovering of extracellular vesicles (EVs), composed of microvesicles (MVs) and exosomes, opened new perspectives to define the modalities of this communication. In the GBM context particularly, we investigated what could be the nature of the EV exchange between GSCs and MSCs. We show that GSCs MVs can activate MSCs into cancer-associated fibroblasts (CAFs)-like cells, that subsequently increase their secretion of exosomes. Moreover, a significant decrease in anti-tumoral miR-100-5p, miR-9-5p and let-7d-5p was observed in these exosomes. This clearly suggests a miRNA-mediated GBM tumor promotion by MSCs exosomes, after their activation by GBM MVs.
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Affiliation(s)
- Delphine Garnier
- CRCINA INSERM U1232, CHU de Nantes, Université de Nantes, 44000 Nantes, France; (E.R.); (J.B.); (P.-F.C.); (L.O.); (F.M.V.)
- LaBCT, Institut de Cancérologie de L’Ouest, 44800 Saint Herblain, France
- Centre de Recherche des Cordeliers, Sorbonne Université, INSERM, Université de Paris, 75006 Paris, France
- Correspondence:
| | - Edward Ratcliffe
- CRCINA INSERM U1232, CHU de Nantes, Université de Nantes, 44000 Nantes, France; (E.R.); (J.B.); (P.-F.C.); (L.O.); (F.M.V.)
- LaBCT, Institut de Cancérologie de L’Ouest, 44800 Saint Herblain, France
| | - Joséphine Briand
- CRCINA INSERM U1232, CHU de Nantes, Université de Nantes, 44000 Nantes, France; (E.R.); (J.B.); (P.-F.C.); (L.O.); (F.M.V.)
- LaBCT, Institut de Cancérologie de L’Ouest, 44800 Saint Herblain, France
| | - Pierre-François Cartron
- CRCINA INSERM U1232, CHU de Nantes, Université de Nantes, 44000 Nantes, France; (E.R.); (J.B.); (P.-F.C.); (L.O.); (F.M.V.)
- LaBCT, Institut de Cancérologie de L’Ouest, 44800 Saint Herblain, France
| | - Lisa Oliver
- CRCINA INSERM U1232, CHU de Nantes, Université de Nantes, 44000 Nantes, France; (E.R.); (J.B.); (P.-F.C.); (L.O.); (F.M.V.)
- LaBCT, Institut de Cancérologie de L’Ouest, 44800 Saint Herblain, France
| | - François M. Vallette
- CRCINA INSERM U1232, CHU de Nantes, Université de Nantes, 44000 Nantes, France; (E.R.); (J.B.); (P.-F.C.); (L.O.); (F.M.V.)
- LaBCT, Institut de Cancérologie de L’Ouest, 44800 Saint Herblain, France
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16
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Osan C, Chira S, Nutu AM, Braicu C, Baciut M, Korban SS, Berindan-Neagoe I. The Connection between MicroRNAs and Oral Cancer Pathogenesis: Emerging Biomarkers in Oral Cancer Management. Genes (Basel) 2021; 12:genes12121989. [PMID: 34946938 PMCID: PMC8700798 DOI: 10.3390/genes12121989] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Revised: 12/09/2021] [Accepted: 12/13/2021] [Indexed: 02/06/2023] Open
Abstract
Oral cancer is a common human malignancy that still maintains an elevated mortality rate despite scientific progress. Tumorigenesis is driven by altered gene expression patterns of proto-oncogenes and tumor-suppressor genes. MicroRNAs, a class of short non-coding RNAs involved in gene regulation, seem to play important roles in oral cancer development, progression, and tumor microenvironment modulation. As properties of microRNAs render them stable in diverse liquid biopsies, together with their differential expression signature in cancer cells, these features place microRNAs at the top of promising biomarkers for diagnostic and prognostic values. In this review, we highlight eight expression levels and functions of the most relevant microRNAs involved in oral cancer development, progression, and microenvironment sustainability. Furthermore, we emphasize the potential of using these small RNA species as non-invasive biomarkers for the early detection of oral cancerous lesions. Conclusively, we highlight the perspectives and limitations of microRNAs as novel diagnostic tools, as well as therapeutic models.
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Affiliation(s)
- Ciprian Osan
- Research Center for Functional Genomics, Biomedicine and Translational Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania; (C.O.); (S.C.); (A.M.N.); (C.B.)
| | - Sergiu Chira
- Research Center for Functional Genomics, Biomedicine and Translational Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania; (C.O.); (S.C.); (A.M.N.); (C.B.)
| | - Andreea Mihaela Nutu
- Research Center for Functional Genomics, Biomedicine and Translational Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania; (C.O.); (S.C.); (A.M.N.); (C.B.)
| | - Cornelia Braicu
- Research Center for Functional Genomics, Biomedicine and Translational Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania; (C.O.); (S.C.); (A.M.N.); (C.B.)
| | - Mihaela Baciut
- Department of Maxillofacial Surgery and Implantology, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400033 Cluj-Napoca, Romania;
| | - Schuyler S. Korban
- Department of Natural Resources & Environmental Sciences, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA;
| | - Ioana Berindan-Neagoe
- Research Center for Functional Genomics, Biomedicine and Translational Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania; (C.O.); (S.C.); (A.M.N.); (C.B.)
- Correspondence:
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17
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Dobre M, Herlea V, Vlăduţ C, Ciocîrlan M, Balaban VD, Constantinescu G, Diculescu M, Milanesi E. Dysregulation of miRNAs Targeting the IGF-1R Pathway in Pancreatic Ductal Adenocarcinoma. Cells 2021; 10:1856. [PMID: 34440625 PMCID: PMC8391367 DOI: 10.3390/cells10081856] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Revised: 07/19/2021] [Accepted: 07/20/2021] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Pancreatic ductal adenocarcinoma (PDAC), the most prevalent neoplastic lethal pancreatic disease, has a poor prognosis and an increasing incidence. The insulin-like growth factor-1 receptor (IGF-1R) signaling pathway is considered to be a contributing factor to the progression, metastasis, and therapy resistance of PDAC. Currently available treatment options for PDAC are limited, but microRNAs (miRNAs) may represent a new therapeutic strategy for targeting genes involved in the IGF-1R signaling pathway. METHOD We investigated the expression levels of 21 miRNAs involved in the IGF-1R signaling pathway in pancreatic tissue from 38 patients with PDAC and 11 controls (five patients with chronic pancreatitis and six patients with normal pancreatic tissue). RESULTS We found 19 differentially expressed miRNAs between the PDAC cases and the controls. In particular, miR-100-5p, miR-145-5p, miR-29c-3p, miR-9-5p, and miR-195-5p were exclusively downregulated in PDAC tissue but not in chronic pancreatitis or normal pancreatic tissues; both control types presented similar levels. We also identified miR-29a-3p, miR-29b-3p, and miR-7-5p as downregulated miRNAs in PDAC tissues as compared with normal tissues but not with pancreatitis tissues. CONCLUSIONS We identified a panel of miRNAs that could represent putative therapeutic targets for the development of new miRNA-based therapies for PDAC.
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Affiliation(s)
- Maria Dobre
- Victor Babes National Institute of Pathology, 050096 Bucharest, Romania; (M.D.); (E.M.)
| | - Vlad Herlea
- Department of Pathology, Fundeni Clinical Institute, 022328 Bucharest, Romania;
| | - Cătălina Vlăduţ
- Department of Gastroenterology, “Prof Dr Agrippa Ionescu” Clinical Emergency Hospital, 011356 Bucharest, Romania;
- Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania; (V.D.B.); (M.D.)
| | - Mihai Ciocîrlan
- Department of Gastroenterology, “Prof Dr Agrippa Ionescu” Clinical Emergency Hospital, 011356 Bucharest, Romania;
- Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania; (V.D.B.); (M.D.)
| | - Vasile Daniel Balaban
- Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania; (V.D.B.); (M.D.)
- Department of Gastroenterology, Carol Davila Central Military Emergency University Hospital, 010825 Bucharest, Romania
| | - Gabriel Constantinescu
- Department of Gastroenterology, Clinical Emergency Hospital Bucharest, 014461 Bucharest, Romania;
| | - Mircea Diculescu
- Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania; (V.D.B.); (M.D.)
- Department of Gastroenterology, Fundeni Clinical Institute, 022328 Bucharest, Romania
| | - Elena Milanesi
- Victor Babes National Institute of Pathology, 050096 Bucharest, Romania; (M.D.); (E.M.)
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18
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Zhang T, Zhu X, Sun Q, Qin X, Zhang Z, Feng Y, Yan M, Chen W. Identification and Confirmation of the miR-30 Family as a Potential Central Player in Tobacco-Related Head and Neck Squamous Cell Carcinoma. Front Oncol 2021; 11:616372. [PMID: 34336638 PMCID: PMC8315965 DOI: 10.3389/fonc.2021.616372] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2020] [Accepted: 03/26/2021] [Indexed: 11/13/2022] Open
Abstract
Constituents of tobacco that can cause DNA adduct formation and oxidative stress are implicated in the development of head and neck squamous cell carcinoma (HNSCC). However, there are few studies on the mechanism(s) that underlie tobacco-associated HNSCC. Here, we used a model in which tumors were induced in rats using 4-nitroquinoline 1-oxide (4NQO), which mimicked tobacco-related HNSCC, and analyzed the expression profiles of microRNAs and mRNAs. Our results indicated that 57 miRNAs and 474 mRNA/EST transcripts exhibited differential expression profiles between tumor and normal tongue tissues. In tumor tissue, the expression levels of rno-miR-30 family members (rno-miR-30a, rno-miR-30a-3p, rno-miR-30b-5p, rno-miR-30c, rno-miR-30d, rno-miR-30e and rno-miR-30e-3p) were only 8% to 37% of those in the control group. The GO terms enrichment analysis of the differentially expressed miRNAs indicated that oxidation reduction was the most enriched process. Low expression of miR-30 family members in human HNSCC cell lines and tissues was validated by qPCR. The results revealed that the expression of miR-30b-5p and miR-30e-5p was significantly decreased in the TCGA HNSCC dataset and validation datasets, and this decrease in expression further distinguishes HNSCC associated with tobacco use from other subtypes of HNSCC. CCK8, colony formation, transwell migration and HNSCC xenograft tumor assays indicated that miR-30b-5p or miR-30e-5p inhibited proliferation, migration and invasion in vitro, and miR-30b-5p suppressed tumor growth in vivo. Moreover, we uncovered that KRAS might be the potential target gene of miR-30e-5p or miR-30b-5p. Thus, our data clearly showed that decreased expression of miR-30e-5p or miR-30b-5p may play a crucial role in cancer development, especially that of tobacco-induced HNSCC, and may be a novel candidate biomarker and target for this HNSCC subtype.
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Affiliation(s)
- Tingting Zhang
- Department of Oral Maxillofacial Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, Shanghai, China.,National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai, China.,Department of Oral and Maxillofacial Surgery, Stomatological Hospital, Tianjin Medical University, Tianjin, China
| | - Xueqin Zhu
- Department of Oral Maxillofacial Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, Shanghai, China.,National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai, China
| | - Qiang Sun
- Department of Oral Maxillofacial Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, Shanghai, China.,National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai, China.,Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Xing Qin
- Department of Oral Maxillofacial Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, Shanghai, China.,National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai, China
| | - Zhen Zhang
- Department of Oral Maxillofacial Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, Shanghai, China.,National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai, China
| | - Yuanyong Feng
- Department of Oral and Maxillofacial Surgery, the Affiliated Hospital of Qingdao University, Qingdao, China
| | - Ming Yan
- Department of Oral Maxillofacial Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, Shanghai, China.,National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai, China
| | - Wantao Chen
- Department of Oral Maxillofacial Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, Shanghai, China.,National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai, China.,Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
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Differentially expressed miR-20, miR-21, miR-100, miR-125a and miR-146a as a potential biomarker for prostate cancer. Mol Biol Rep 2021; 48:3349-3356. [PMID: 33948855 DOI: 10.1007/s11033-021-06384-z] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2020] [Accepted: 04/24/2021] [Indexed: 12/19/2022]
Abstract
Prostate cancer is the leading cause of death among men worldwide. Deregulation of microRNAs has been reported in many cancers. Expression of microRNAs miR-20a-5p, miR-21-5p, miR-100-5p, miR-125a-5p and miR-146a-5p in tissue blocks of histologically confirmed prostate cancer patients compared with BPH patients, to identify potential microRNA biomarker for prostate cancer. MicroRNA was isolated and expression was quantified by qRT-PCR using Taqman Advanced microRNA assay kits. The interactions between the microRNA:target mRNA were predicted by using bioinformatics tools such as miRwalk and miRTargetlink. The experimentally validated targets were analysed using gprofiler to identify their molecular function, biological process and related pathways. The expression analysis revealed that miR-21 and miR-100 were significantly down-regulated whereas miR-125a was up-regulated in prostate cancer patients. Comparative analysis of the expression levels with tumor grading reveal that miR-100 was significantly down-regulated (p < 0.05) in high grade tumor, indicating that miR-100 associated with prostate cancer. ROC analysis revealed that combined analysis of down-regulated miRNAs (miR-21 and miR-100) shown AUC of 0.72 (95% CI 0.65-0.79). The combined analysis of all five miRNAs showed AUC of 0.87 (95% CI 0.81-0.92). The targets prediction analysis revealed several validated targets including BCL2, ROCK1, EGFR, PTEN, MTOR, NAIF1 and VEGFA. Our results provide evidence that combined analysis of all the five miRNAs as a panel can significantly improve the prediction level of the presence of prostate cancer and may be used as a potential diagnostic biomarker.
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Masaoka T, Shinozuka K, Ohara K, Tsuda H, Imai K, Tonogi M. Bioinformatics analysis of dysregulated exosomal microRNAs derived from oral squamous cell carcinoma cells. J Oral Sci 2021; 63:174-178. [PMID: 33731508 DOI: 10.2334/josnusd.20-0662] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
PURPOSE The present study aimed to identify dysregulated exosomal miRNAs associated with diagnostic and therapeutic biomarkers in oral squamous cell carcinoma (OSCC). METHODS Microarray analysis was used to compare expression profiles of exosomal miRNAs in the OSCC-derived cell lines HSC-2, HSC-3, Ca9-22, and HO-1-N1 with those in human normal keratinocytes (HNOKs). The identified OSCC-related miRNAs and their potential target genes were analyzed with bioinformatic analyses, and the data were subjected to Ingenuity Pathway Analysis (IPA) to clarify functional networks and gene ontologies of the identified exosomal miRNAs secreted by OSCC cells. RESULTS Comparison with HNOKs detected 8 upregulated and 12 downregulated miRNAs in OSCC-secreted exosomes. The potential target mRNAs of these dysregulated miRNAs were suggested by IPA, and 6 significant genetic networks were indicated by genetic network analysis. Furthermore, 4 crucial upstream miRNAs-miR-125b-5p, miR-17-5p, miR-200b-3p, and miR-23a-3p-were identified. miR-125b-5p was a central node in the most significant network. Gene ontology analysis showed significant enrichment of genes with cancer-related functions, such as molecular mechanisms of cancer, cell cycle, and regulation of the epithelial-mesenchymal transition. CONCLUSION These results provide a comprehensive view of the functions of dysregulated exosomal miRNAs in OSCC, thus illuminating OSCC tumorigenesis and development.
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Affiliation(s)
- Tadashi Masaoka
- Division of Oral Structural and Functional Biology, Nihon University Graduate School of Dentistry
| | - Keiji Shinozuka
- Department of Oral and Maxillofacial Surgery, Nihon University School of Dentistry.,Department of Plastic, Oral and Maxillofacial Surgery, School of Medicine, Teikyo University
| | - Kenshin Ohara
- Department of Plastic, Oral and Maxillofacial Surgery, School of Medicine, Teikyo University
| | - Hiromasa Tsuda
- Department of Biochemistry, Nihon University School of Dentistry
| | - Kenichi Imai
- Department of Microbiology, Nihon University School of Dentistry
| | - Morio Tonogi
- Department of Oral and Maxillofacial Surgery, Nihon University School of Dentistry
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MiR-125b-2 knockout increases high-fat diet-induced fat accumulation and insulin resistance. Sci Rep 2020; 10:21969. [PMID: 33319811 PMCID: PMC7738482 DOI: 10.1038/s41598-020-77714-7] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2020] [Accepted: 11/09/2020] [Indexed: 12/26/2022] Open
Abstract
Obese individuals are more susceptible to comorbidities than individuals of healthy weight, including cardiovascular disease and metabolic disorders. MicroRNAs are a class of small and noncoding RNAs that are implicated in the regulation of chronic human diseases. We previously reported that miR-125b plays a critical role in adipogenesis in vitro. However, the involvement of miR-125b-2 in fat metabolism in vivo remains unknown. In the present study, miR-125b-2 knockout mice were generated using CRISPR/CAS9 technology, resulting in mice with a 7 bp deletion in the seed sequence of miR-125b-2. MiR-125b-2 knockout increased the weight of liver tissue, epididymal white fat and inguinal white fat. MiR-125b-2 knockout also increased adipocyte volume in HFD-induced obese mice, while there were no significant differences in body weight and feed intake versus mice fed a normal diet. Additionally, qRT-PCR and western blot analysis revealed that the expression of the miR-125b-2 target gene SCD-1 and fat synthesis-associated genes, such as PPARγ and C/EBPα, were significantly up-regulated in miR-125b-2KO mice (P < 0.05). Moreover, miR-125b-2KO altered HFD-induced changes in glucose tolerance and insulin resistance. In conclusion, we show that miR-125b-2 is a novel potential target for regulating fat accumulation, and also a candidate target to develop novel treatment strategies for obesity and diabetes.
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Vishwakarma S, Pandey R, Singh R, Gothalwal R, Kumar A. Expression of H19 long non-coding RNA is down-regulated in oral squamous cell carcinoma. J Biosci 2020. [DOI: 10.1007/s12038-020-00118-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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Eniafe J, Jiang S. MicroRNA-99 family in cancer and immunity. WILEY INTERDISCIPLINARY REVIEWS-RNA 2020; 12:e1635. [PMID: 33230974 DOI: 10.1002/wrna.1635] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/31/2020] [Revised: 11/02/2020] [Accepted: 11/04/2020] [Indexed: 12/19/2022]
Abstract
The microRNA (miR)-99 family comprising miR-99a, miR-99b, and miR-100 is an evolutionarily conserved family with existence dating prior to the bilaterians. Members are typically oncogenic in leukemia while their functional roles in other cancers alternate between that of a tumor suppressor and a tumor promoter. Targets of the miR-99 family rank in the lists of oncogenes and tumor suppressors, thereby illustrating the dual role of this miR family as oncogenic miRs (oncomiRs) and tumor suppressing miRs (TSmiRs) in different cellular contexts. In addition to their functional roles in cancers, miR-99 family is implicated in the modulation of macrophage inflammatory responses and T-cell subsets biology, thereby exerting critical roles in the maintenance of tissue homeostasis, establishment of peripheral tolerance as well as resolution of an inflammatory reaction. Here, we review emerging knowledge of this miR family and discuss remaining concerns linked to their activities. A better dissection of the functional roles of miR-99 family members in cancer and immunity will help in the development of novel miR-99-based therapeutics for the treatment of human cancer and immune-related diseases. This article is categorized under: RNA in Disease and Development > RNA in Disease.
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Affiliation(s)
- Joseph Eniafe
- Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, Shreveport, Louisiana, USA
| | - Shuai Jiang
- Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, Shreveport, Louisiana, USA
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Le F, Ou Y, Luo P, Zhong X. LncRNA NCK1-AS1 in plasma distinguishes oral ulcer from early-stage oral squamous cell carcinoma. ACTA ACUST UNITED AC 2020; 27:16. [PMID: 33194849 PMCID: PMC7656691 DOI: 10.1186/s40709-020-00126-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2020] [Accepted: 09/23/2020] [Indexed: 12/18/2022]
Abstract
Background Oral squamous cell carcinoma (OSCC) at early stages can be misdiagnosed as an oral ulcer (OU) due to similar symptoms, such as chronic and indurated ulcer. LncRNA NCK1-AS1 has been characterized as a key player in cervical cancer, while its role in OSCC is unknown. Methods All participants were selected at Jiangxi Province Tumor Hospital from December 2016 to December 2018. Expression levels of NCK1-AS1 and miR-100 in plasma from both OSCC and OU patients were measured by RT-qPCR. Diagnostic analysis was performed through ROC curve. Potential interactions between NCK1-AS1 and miR-100 were detected by cell transfection experiments. Cell invasion and migration were assessed by Transwell assays. Results The expression of NCK1-AS1 was upregulated in early-stage OSCC patients but not in OU patients. Upregulation of NCK1-AS1 distinguished OSCC patients from OU patients. The expression of miR-100 was inversely correlated with the expression of NCK1-AS1. Overexpression of NCK1-AS1 was followed by promoted OSCC cell invasion and migration. Overexpression of miR-100 did not affect the expression of NCK1-AS1 but inhibited the role of NCK1-AS1. Conclusions Therefore, NCK1-AS1 may promote the metastasis of OSCC by downregulating miR-100.
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Affiliation(s)
- Fei Le
- Department of Head and Neck Surgery, Jiangxi Province Tumor Hospital, Nanchang City, Jiangxi Province 330029 People's Republic of China
| | - Yangqian Ou
- Department of Intensive Medicine, Jiangxi Province Tumor Hospital, Nanchang City, Jiangxi Province 330029 People's Republic of China
| | - Ping Luo
- Department of Surgical Oncology, Nanchang Third Hospital, Nanchang City, Jiangxi Province 330002 People's Republic of China
| | - Xiaoming Zhong
- Department of Radiotherapy, Jiangxi Province Tumor Hospital, No.519 Beijing East Road, Nanchang City, Jiangxi Province 330029 People's Republic of China
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Yete S, Saranath D. MicroRNAs in oral cancer: Biomarkers with clinical potential. Oral Oncol 2020; 110:105002. [PMID: 32949853 DOI: 10.1016/j.oraloncology.2020.105002] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2020] [Revised: 08/13/2020] [Accepted: 09/04/2020] [Indexed: 02/08/2023]
Abstract
Oral cancer is the sixteenth most common cancer globally, with a relatively poor five-year survival rate of 50%. Thus it is imperative to understand the biology of oral cancer and examine alternative prognostic and therapeutic targets for oral cancer. MicroRNAs (miRNAs) are small non-coding RNAs mediating gene expression at the post-transcriptional level through mRNA degradation or translational repression. miRNAs play an essential role in cancer development and oncogenic cell processes. miRNA deregulation is observed in oral cancer and associated with prognosis. However, the role of miRNAs and their clinical implications in oral cancer is not clear. The current review highlights the miRNA profile of oral cancer and discusses the diagnostic, prognostic and potential therapeutic targets with clinical implications. miRNAs mediate activation or suppression of signalling pathways associated with oral cancer. Hence, a panel of select deregulated miRNAs may indicate clinicopathological features, personalised treatment outcome and provide novel lead profiles of oral cancer. The translational applications of miRNAs may lead to better management and survival of oral cancer patients. The compiled data provides a platform for consideration of miRNA signatures as potential biomarkers for early oral cancer diagnosis, prognosis and as novel molecular therapies.
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Affiliation(s)
- Subuhi Yete
- Cancer Patients Aid Association, Dr. Vithaldas Parmar Research & Medical Centre, Sumer Kendra, Worli, Mumbai 400018, India
| | - Dhananjaya Saranath
- Cancer Patients Aid Association, Dr. Vithaldas Parmar Research & Medical Centre, Sumer Kendra, Worli, Mumbai 400018, India.
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Figueroa-González G, Carrillo-Hernández JF, Perez-Rodriguez I, Cantú de León D, Campos-Parra AD, Martínez-Gutiérrez AD, Coronel-Hernández J, García-Castillo V, López-Camarillo C, Peralta-Zaragoza O, Jacobo-Herrera NJ, Guardado-Estrada M, Pérez-Plasencia C. Negative Regulation of Serine Threonine Kinase 11 (STK11) through miR-100 in Head and Neck Cancer. Genes (Basel) 2020; 11:1058. [PMID: 32911741 PMCID: PMC7563199 DOI: 10.3390/genes11091058] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2020] [Revised: 08/18/2020] [Accepted: 08/25/2020] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Serine Threonine Kinase 11 (STK11), also known as LKB1, is a tumor suppressor gene that regulates several biological processes such as apoptosis, energetic metabolism, proliferation, invasion, and migration. During malignant progression, different types of cancer inhibit STK11 function by mutation or epigenetic inactivation. In Head and Neck Cancer, it is unclear what mechanism is involved in decreasing STK11 levels. Thus, the present work aims to determine whether STK11 expression might be regulated through epigenetic or post-translational mechanisms. METHODS Expression levels and methylation status for STK11 were analyzed in 59 cases of head and neck cancer and 10 healthy tissue counterparts. Afterward, we sought to identify candidate miRNAs exerting post-transcriptional regulation of STK11. Then, we assessed a luciferase gene reporter assay to know if miRNAs directly target STK11 mRNA. The expression levels of the clinical significance of mir-100-3p, -5p, and STK11 in 495 HNC specimens obtained from the TCGA database were further analyzed. Finally, the Kaplan-Meier method was used to estimate the prognostic significance of the miRNAs for Overall Survival, and survival curves were compared through the log-rank test. RESULTS STK11 was under-expressed, and its promoter region was demethylated or partially methylated. miR-17-5p, miR-106a-5p, miR-100-3p, and miR-100-5p could be negative regulators of STK11. Our experimental data suggested evidence that miR-100-3p and -5p were over-expressed in analyzed tumor patient samples. Luciferase gene reporter assay experiments showed that miR-100-3p targets and down-regulates STK11 mRNA directly. With respect to overall survival, STK11 expression level was significant for predicting clinical outcomes. CONCLUSION This is, to our knowledge, the first report of miR-100-3p targeting STK11 in HNC. Together, these findings may support the importance of regulation of STK11 through post-transcriptional regulation in HNC and the possible contribution to the carcinogenesis process in this neoplasia.
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Affiliation(s)
- Gabriela Figueroa-González
- Unidad Multidisciplinaria de Investigación Experimental Zaragoza (UMIEZ), Facultad de Estudios Superiores Zaragoza, Universidad Nacional Autónoma de México, Mexico City 09230, Mexico;
- Unidad de Investigación Biomédica en Cáncer, Laboratorio de Genómica, Instituto Nacional de Cancerología, Mexico City 14080, Mexico; (J.F.C.-H.); (I.P.-R.); (D.C.d.L.); (A.D.C.-P.); (A.D.M.-G.); (J.C.-H.)
| | - José F. Carrillo-Hernández
- Unidad de Investigación Biomédica en Cáncer, Laboratorio de Genómica, Instituto Nacional de Cancerología, Mexico City 14080, Mexico; (J.F.C.-H.); (I.P.-R.); (D.C.d.L.); (A.D.C.-P.); (A.D.M.-G.); (J.C.-H.)
| | - Itzel Perez-Rodriguez
- Unidad de Investigación Biomédica en Cáncer, Laboratorio de Genómica, Instituto Nacional de Cancerología, Mexico City 14080, Mexico; (J.F.C.-H.); (I.P.-R.); (D.C.d.L.); (A.D.C.-P.); (A.D.M.-G.); (J.C.-H.)
| | - David Cantú de León
- Unidad de Investigación Biomédica en Cáncer, Laboratorio de Genómica, Instituto Nacional de Cancerología, Mexico City 14080, Mexico; (J.F.C.-H.); (I.P.-R.); (D.C.d.L.); (A.D.C.-P.); (A.D.M.-G.); (J.C.-H.)
| | - Alma D. Campos-Parra
- Unidad de Investigación Biomédica en Cáncer, Laboratorio de Genómica, Instituto Nacional de Cancerología, Mexico City 14080, Mexico; (J.F.C.-H.); (I.P.-R.); (D.C.d.L.); (A.D.C.-P.); (A.D.M.-G.); (J.C.-H.)
| | - Antonio D. Martínez-Gutiérrez
- Unidad de Investigación Biomédica en Cáncer, Laboratorio de Genómica, Instituto Nacional de Cancerología, Mexico City 14080, Mexico; (J.F.C.-H.); (I.P.-R.); (D.C.d.L.); (A.D.C.-P.); (A.D.M.-G.); (J.C.-H.)
| | - Jossimar Coronel-Hernández
- Unidad de Investigación Biomédica en Cáncer, Laboratorio de Genómica, Instituto Nacional de Cancerología, Mexico City 14080, Mexico; (J.F.C.-H.); (I.P.-R.); (D.C.d.L.); (A.D.C.-P.); (A.D.M.-G.); (J.C.-H.)
| | - Verónica García-Castillo
- Unidad de Investigación Biomédica en Cáncer, Laboratorio de Genómica del Cáncer, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla 54090, Edo.Mex, Mexico;
| | - César López-Camarillo
- Posgrado en Ciencias Genómicas, Universidad Autónoma de la Ciudad de México, Mexico City 09790, Mexico;
| | - Oscar Peralta-Zaragoza
- Dirección de Infecciones Crónicas y Cáncer, Centro de Investigación Sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública, Cuernavaca 62100, Morelos, Mexico;
| | - Nadia J. Jacobo-Herrera
- Unidad de Bioquímica, Instituto Nacional de Nutrición y Ciencias Médicas, Salvador Zubirán, Mexico City 14000, Mexico;
| | - Mariano Guardado-Estrada
- Laboratorio de Genética, Licenciatura en Ciencia Forense, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City 04360, Mexico;
| | - Carlos Pérez-Plasencia
- Unidad de Investigación Biomédica en Cáncer, Laboratorio de Genómica, Instituto Nacional de Cancerología, Mexico City 14080, Mexico; (J.F.C.-H.); (I.P.-R.); (D.C.d.L.); (A.D.C.-P.); (A.D.M.-G.); (J.C.-H.)
- Unidad de Investigación Biomédica en Cáncer, Laboratorio de Genómica del Cáncer, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla 54090, Edo.Mex, Mexico;
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Lu X, Gan Q, Gan C, Zheng Y, Cai B, Li X, Li D, Yin G. Long non-coding RNA PICSAR knockdown inhibits the progression of cutaneous squamous cell carcinoma by regulating miR-125b/YAP1 axis. Life Sci 2020; 274:118303. [PMID: 32841663 DOI: 10.1016/j.lfs.2020.118303] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2020] [Revised: 06/30/2020] [Accepted: 08/17/2020] [Indexed: 01/22/2023]
Abstract
AIMS The purpose of this study was to explore the precise role and mechanism of p38 inhibiting cutaneous squamous cell carcinoma associated lincRNA (PICSAR) in CSCC. MATERIALS AND METHODS The expression levels of PICSAR, microRNA-125b (miR-125b) and yes-associated protein1 (YAP1) were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation, apoptosis and invasion were evaluated by Cell Counting Kit-8 (CCK-8) assay, flow cytometry, transwell assay, respectively. The interaction between miR-125b and PICSAR or YAP1 was predicted by bioinformatics software and confirmed by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Western blot was employed to detect the protein expression of YAP1. The mice xenograft model was established to investigate the role of PICSAR in vivo. KEY FINDINGS PICSAR was upregulated in CSCC tissues and cells. PICSAR knockdown inhibited cell proliferation and invasion and induced apoptosis in CSCC cells. Moreover, miR-125b could directly bind to PICSAR and its inhibition reversed the effect of PICSAR knockdown on proliferation, invasion and apoptosis in CSCC cells. In addition, YAP1 was a direct target of miR-125b and its overexpression attenuated the anti-cancer role of miR-125b in CSCC cells. Furthermore, YAP1 expression was positively regulated by PICSAR and negatively regulated by miR-125b. Besides, interference of PICSAR suppressed tumor growth by upregulating miR-125b and downregulating YAP1. SIGNIFICANCE PICSAR knockdown suppressed cell proliferation and invasion and promoted apoptosis in CSCC cells by regulating miR-125b/YAP1 axis, providing new sights for treatment of CSCC.
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Affiliation(s)
- Xiaoyan Lu
- Department of Dermatology, Xinxiang Central Hospital, Xinxiang, Henan, China
| | - Quan Gan
- Department of Dermatology, Xinxiang Central Hospital, Xinxiang, Henan, China
| | - Caibin Gan
- Department of Dermatology, Xinxiang Central Hospital, Xinxiang, Henan, China
| | - Yunpeng Zheng
- Department of Dermatology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Bingjie Cai
- Department of Dermatology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Xuyang Li
- Department of Dermatology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Dongqin Li
- Department of Dermatology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Guangwen Yin
- Department of Dermatology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
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Aali M, Mesgarzadeh AH, Najjary S, Abdolahi HM, Kojabad AB, Baradaran B. Evaluating the role of microRNAs alterations in oral squamous cell carcinoma. Gene 2020; 757:144936. [PMID: 32640301 DOI: 10.1016/j.gene.2020.144936] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2020] [Revised: 05/31/2020] [Accepted: 07/01/2020] [Indexed: 12/16/2022]
Abstract
Oral squamous cell carcinoma (OSCC) accounts for nearly 90 percent of oral cavity malignancies and is one of the most widespread oral cancers in the world. The microRNAs (miRNAs or miRs) have an important role in cellular processes comprising cell cycle, differentiation, and also apoptosis. MiRNAs are also implicated in the progression of cancers, including OSCC, through a variety of signaling pathways. One of the most significant signaling pathways in OSCC is the PI3K / Akt pathway that has been illustrated to be under the tight regulation of miRNAs. Deregulation or activation of the PI3K / Akt pathway due to mutations has been revealed to be implicated in the development of oral cancer. According to studies, more than 47% of HNSCC and around 38% of OSCC samples indicate at least one molecular alteration in this signaling pathway. The potential of miRNAs for their use as therapeutic tools in the diagnosis as well as treatment of numerous diseases have been confirmed. In the current review, we summarize miRNAs and their possible mechanisms as well as their functions in OSCC advancement and progression.
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Affiliation(s)
- Mehdi Aali
- Department of Oral and Maxillofacial Surgery, School of Dentistry, Tabriz University of Medical Sciences, Tabriz, Iran; Dental and Periodontal Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Ali Hossein Mesgarzadeh
- Department of Oral and Maxillofacial Surgery, School of Dentistry, Tabriz University of Medical Sciences, Tabriz, Iran; Dental and Periodontal Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Shiva Najjary
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Hossein Mashhadi Abdolahi
- Tabriz Health Services Management Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Behzad Baradaran
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
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Zhang H, Yang K, Ren T, Huang Y, Liang X, Yu Y, Wang W, Niu J, Lou J, Tang X, Guo W. miR-100-5p Inhibits Malignant Behavior of Chordoma Cells by Targeting IGF1R. Cancer Manag Res 2020; 12:4129-4137. [PMID: 32606920 PMCID: PMC7293400 DOI: 10.2147/cmar.s252185] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2020] [Accepted: 05/13/2020] [Indexed: 12/27/2022] Open
Abstract
Purpose Our research aimed to illuminate the role of miR-100-5p in chordoma and potential mechanism. Materials and Methods We used microRNA array analysis to explore differentially expressed miRNAs in chordoma tissue and then verified by qRT-PCR. Cell proliferation and transwell assay were used to evaluate the function of miR-100-5p. Cell apoptosis was analyzed by flow cytometry, and using biological software, we predicted that the insulin-like growth factor 1 receptor (IGF1R) could be the target gene of miR-100-5p, which was then validated by dual luciferase assays and Western blot. Results miR-100-5p was downregulated in chordoma tissues. Overexpression of miR-100-5p could suppress the growth of chordoma both in vitro and in vivo, and miR-100-5p could inhibit the migration and invasion of chordoma cells partially by suppressing epithelial–mesenchymal transition (EMT). Furthermore, IGF1R was validated as the target gene of miR-100-5p and expressed in most chordoma tissues. Conclusion In conclusion, our results showed that miR-100-5p was lowly expressed in chordoma and inhibited tumor malignant progression by targeting IGF1R.
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Affiliation(s)
- Hongliang Zhang
- Musculoskeletal Tumor Center, Peking University People's Hospital, Beijing, People's Republic of China.,Beijing Key Laboratory of Musculoskeletal Tumor, Beijing, People's Republic of China
| | - Kang Yang
- Department of Orthopedics, Yangzhou University Affiliated Hospital, Yangzhou, People's Republic of China
| | - Tingting Ren
- Musculoskeletal Tumor Center, Peking University People's Hospital, Beijing, People's Republic of China.,Beijing Key Laboratory of Musculoskeletal Tumor, Beijing, People's Republic of China
| | - Yi Huang
- Musculoskeletal Tumor Center, Peking University People's Hospital, Beijing, People's Republic of China.,Beijing Key Laboratory of Musculoskeletal Tumor, Beijing, People's Republic of China
| | - Xin Liang
- Musculoskeletal Tumor Center, Peking University People's Hospital, Beijing, People's Republic of China.,Beijing Key Laboratory of Musculoskeletal Tumor, Beijing, People's Republic of China
| | - Yiyang Yu
- Musculoskeletal Tumor Center, Peking University People's Hospital, Beijing, People's Republic of China.,Beijing Key Laboratory of Musculoskeletal Tumor, Beijing, People's Republic of China
| | - Wei Wang
- Musculoskeletal Tumor Center, Peking University People's Hospital, Beijing, People's Republic of China.,Beijing Key Laboratory of Musculoskeletal Tumor, Beijing, People's Republic of China
| | - Jianfang Niu
- Musculoskeletal Tumor Center, Peking University People's Hospital, Beijing, People's Republic of China.,Beijing Key Laboratory of Musculoskeletal Tumor, Beijing, People's Republic of China
| | - Jingbing Lou
- Musculoskeletal Tumor Center, Peking University People's Hospital, Beijing, People's Republic of China.,Beijing Key Laboratory of Musculoskeletal Tumor, Beijing, People's Republic of China
| | - Xiaodong Tang
- Musculoskeletal Tumor Center, Peking University People's Hospital, Beijing, People's Republic of China.,Beijing Key Laboratory of Musculoskeletal Tumor, Beijing, People's Republic of China
| | - Wei Guo
- Musculoskeletal Tumor Center, Peking University People's Hospital, Beijing, People's Republic of China.,Beijing Key Laboratory of Musculoskeletal Tumor, Beijing, People's Republic of China
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Liu P, Zhong Y, Cao T, Sheng X, Huang H. A frequent somatic mutation in the 3'UTR of GAPDH facilitates the development of ovarian cancer by creating a miR‑125b binding site. Oncol Rep 2020; 44:887-896. [PMID: 32705257 PMCID: PMC7388293 DOI: 10.3892/or.2020.7663] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2019] [Accepted: 04/23/2020] [Indexed: 12/27/2022] Open
Abstract
Ovarian cancer (OVCA) is one of the most common types of cancer in women worldwide. Recent studies have focused on the presence and effect of somatic mutations in patients with OVCA; however, studies on the roles of mutations located in the untranslated regions (UTR) of genes in OVCA remain limited. In the present study, a frequent somatic mutation in the glyceraldehyde 3-phosphate dehydrogenase (GADPH) 3′UTR was identified using transcriptome sequencing of 120 pairs of OVCA tissue samples. The mutant GAPDH 3′UTR promoted tumor growth and cell motility. Furthermore, the mutation in the GAPDH 3′UTR significantly downregulated the levels of mature miR-125b by creating a new miR-125b binding site. Finally, STAT3 levels were increased in SKOV3 cells stably expressing the mutant GADPH 3′UTR, which is a critical target gene of miR-125b. In conclusion, the present study demonstrated that the mutation located in GAPDH 3′UTR promoted OVCA growth and development by sponging miR-125b and thereby affecting STAT3 expression levels.
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Affiliation(s)
- Peisen Liu
- Key Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510150, P.R. China
| | - Yumin Zhong
- Key Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510150, P.R. China
| | - Ting Cao
- Key Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510150, P.R. China
| | - Xiujie Sheng
- Key Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510150, P.R. China
| | - Huang Huang
- Key Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510150, P.R. China
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31
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Mohammad Hoseini Azar MR, Shanehbandi D, Mansouri M, Pashaei Sarand S, Asadi M, Akbari M, Sadeghzadeh M, Abolghasemi M, Poursaei E, Gasembaglou S. Altered expression levels of miR-212, miR-133b and miR-27a in tongue squamous cell carcinoma (TSCC) with clinicopathological considerations. GENE REPORTS 2020. [DOI: 10.1016/j.genrep.2020.100622] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
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32
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Ghosh RD, Pattatheyil A, Roychoudhury S. Functional Landscape of Dysregulated MicroRNAs in Oral Squamous Cell Carcinoma: Clinical Implications. Front Oncol 2020; 10:619. [PMID: 32547936 PMCID: PMC7274490 DOI: 10.3389/fonc.2020.00619] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2019] [Accepted: 04/03/2020] [Indexed: 12/24/2022] Open
Abstract
MicroRNA (miRNA) dysregulation is associated with the pathogenesis of oral squamous cell carcinoma (OSCC), and its elucidation could potentially provide information on patient outcome. A growing body of translational research on miRNA biology is focusing on precision oncology, aiming to decode the miRNA regulatory network in the development and progression of cancer. Tissue-specific expression and stable presence in all body fluids are unique features of miRNAs, which could be potentially exploited in the clinical setting. Recent understanding of miRNA properties has led them to be useful, attractive, and potential tools either as biomarkers (distinct miRNA expression signature) for diagnosis and prognostic outcomes or as targets for novel therapeutic entities, enabling personalized treatment for OSCC. In this review, we discuss recent research on different aspects of alterations in miRNA profiles along with their clinical significance and strive to identify probable potential miRNA biomarkers for diagnosis and prognosis of OSCC. We also discuss the current understanding and scope of development of miRNA-based therapeutics against OSCC.
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Affiliation(s)
- Ruma Dey Ghosh
- Tata Translational Cancer Research Center, Tata Medical Center, Kolkata, India
| | - Arun Pattatheyil
- Department of Head and Neck Surgical Oncology, Tata Medical Center, Kolkata, India
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33
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Irani S, Barati I, Badiei M. Periodontitis and oral cancer - current concepts of the etiopathogenesis. Oncol Rev 2020; 14:465. [PMID: 32231765 PMCID: PMC7097927 DOI: 10.4081/oncol.2020.465] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2019] [Accepted: 02/12/2020] [Indexed: 02/06/2023] Open
Abstract
Gingival tissues are attacked by oral pathogens which can induce inflammatory reactions. The immune-inflammatory responses play essential roles in the patient susceptibility to periodontal diseases. There is a wealth of evidence indicating a link between chronic inflammation and risk of malignant transformation of the affected oral epithelium. Periodontitis is associated with an increased risk of developing chronic systemic conditions including autoimmune diseases and different types of cancers. Besides, some risk factors such as smoking, alcohol consumption and human papilloma virus have been found to be associated with both periodontitis and oral cancer. This review article aimed to study the current concepts in pathogenesis of chronic periodontitis and oral cancer by reviewing the related articles.
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Affiliation(s)
- Soussan Irani
- Dental Research Centre, Oral Pathology Department, Dental Faculty, Hamadan University of Medical Sciences
| | - Iman Barati
- Department of Periodontology, Dental Faculty, Hamadan University of Medical Sciences
| | - Mohammadreza Badiei
- Dental Student, Dental Faculty, Hamadan University of Medical Sciences, Hamadan, Iran
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34
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IKKβ overexpression together with a lack of tumour suppressor genes causes ameloblastic odontomas in mice. Int J Oral Sci 2020; 12:1. [PMID: 31900382 PMCID: PMC6946653 DOI: 10.1038/s41368-019-0067-9] [Citation(s) in RCA: 106] [Impact Index Per Article: 21.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2019] [Accepted: 10/14/2019] [Indexed: 12/18/2022] Open
Abstract
Odontogenic tumours are a heterogeneous group of lesions that develop in the oral cavity region and are characterized by the formation of tumoural structures that differentiate as teeth. Due to the diversity of their histopathological characteristics and clinical behaviour, the classification of these tumours is still under debate. Alterations in morphogenesis pathways such as the Hedgehog, MAPK and WNT/β-catenin pathways are implicated in the formation of odontogenic lesions, but the molecular bases of many of these lesions are still unknown. In this study, we used genetically modified mice to study the role of IKKβ (a fundamental regulator of NF-κB activity and many other proteins) in oral epithelial cells and odontogenic tissues. Transgenic mice overexpressing IKKβ in oral epithelial cells show a significant increase in immune cells in both the oral epithelia and oral submucosa. They also show changes in the expression of several proteins and miRNAs that are important for cancer development. Interestingly, we found that overactivity of IKKβ in oral epithelia and odontogenic tissues, in conjunction with the loss of tumour suppressor proteins (p53, or p16 and p19), leads to the appearance of odontogenic tumours that can be classified as ameloblastic odontomas, sometimes accompanied by foci of secondary ameloblastic carcinomas. These tumours show NF-κB activation and increased β-catenin activity. These findings may help to elucidate the molecular determinants of odontogenic tumourigenesis and the role of IKKβ in the homoeostasis and tumoural transformation of oral and odontogenic epithelia.
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35
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Lampropoulou DI, Aravantinos G, Laschos K, Theodosopoulos T, Papadimitriou C, Gazouli M. MiR-218 and miR-100 polymorphisms as markers of irinotecan-based chemotherapy response in metastatic colorectal cancer. Int J Colorectal Dis 2019; 34:1871-1877. [PMID: 31598748 DOI: 10.1007/s00384-019-03401-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/10/2019] [Indexed: 02/04/2023]
Abstract
PURPOSE Colorectal cancer is the fourth cause of cancer-related death. Drug toxicity and resistance remain concerns of major importance. miR-100 and miR-218 are micro-RNAs that regulate cellular proliferation, differentiation and apoptosis acting as oncogenes and tumour suppressors; their functions and have been linked with toxicity development and drug resistance. METHODS We investigated the correlation between rs11134527 miR-218 and rs1834306 miR-100 polymorphisms and irinotecan-based regimens with regard to drug efficacy and toxicity. A total of 105 mCRC patients receiving irinotecan-based regimens were included in our study and assessed in terms of toxicity development and response to treatment. Rs11134527 miR-218 and rs1834306 miR-100 polymorphism genotyping in the peripheral blood was performed with PCR-RFLP. RESULTS Neither rs11134527 miR-218 nor rs1834306 miR-100 are associated with toxicity risk to treatment regimens. GA/AA genotypes of rs11134527 and CT/TT genotypes of rs1834306 were associated with a significantly reduced time-to-progression (TTP) and overall survival (OS). CONCLUSIONS GA/AA genotypes of rs11134527 miR-218 and CT/TT genotypes of rs1834306 miR-100 polymorphisms could serve as prognostic biomarkers of TTP and OS. Carriers of the A allele of the miR-218 rs11134527 and T allele of the miR-100 rs1834306 polymorphisms are more likely not to respond to irinotecan-based therapies. However, further studies in larger patient populations are required.
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Affiliation(s)
- Dimitra-Ioanna Lampropoulou
- Second Department of Medical Oncology, General Oncology Hospital of Kifissia "Agioi Anargiroi", Athens, Greece
| | - Gerasimos Aravantinos
- Second Department of Medical Oncology, General Oncology Hospital of Kifissia "Agioi Anargiroi", Athens, Greece
| | - Konstantinos Laschos
- Second Department of Medical Oncology, General Oncology Hospital of Kifissia "Agioi Anargiroi", Athens, Greece
| | - Theodosis Theodosopoulos
- Second Department of Surgery, Aretaieion Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Christos Papadimitriou
- Second Department of Surgery, Aretaieion Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Maria Gazouli
- Laboratory of Biology, Medical School, National and Kapodistrian University of Athens, Michalakopoulou 176, 11527, Athens, Greece.
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36
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Irani S. Emerging insights into the biology of metastasis: A review article. IRANIAN JOURNAL OF BASIC MEDICAL SCIENCES 2019; 22:833-847. [PMID: 31579438 PMCID: PMC6760483 DOI: 10.22038/ijbms.2019.32786.7839] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/17/2018] [Accepted: 02/16/2019] [Indexed: 12/12/2022]
Abstract
Metastasis means the dissemination of the cancer cells from one organ to another which is not directly connected to the primary site. Metastasis has a crucial role in the prognosis of cancer patients. A few theories, different types of cell and several molecular pathways have been proposed to explain the mechanism of metastasis. In this work, the related articles in the limited period of time, 2000-mid -2018 were reviewed, through search in PubMed, Google Scholar and Scopus database. The articles published in the last two decades related to the biology of cancer metastasis were selected and the most important factors were discussed. Metastasis is critical factor to predict survival in patients with advanced cancer and prognosis determines the treatment plan. Many different cell types and various signaling pathways control the metastatic process. Metastasis is a multistep process. Many signaling pathways and molecules are involved in metastasis. Increasing knowledge about the mechanism of metastasis can help in finding the promising targets of cancer therapy.
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Affiliation(s)
- Soussan Irani
- Dental Research Centre, Oral Pathology Department, Dental Faculty, Hamadan University of Medical Sciences, Hamadan,Iran, Lecturer at Griffith University, Gold Coast, Australia
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37
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Jakob M, Mattes LM, Küffer S, Unger K, Hess J, Bertlich M, Haubner F, Ihler F, Canis M, Weiss BG, Kitz J. MicroRNA expression patterns in oral squamous cell carcinoma: hsa-mir-99b-3p and hsa-mir-100-5p as novel prognostic markers for oral cancer. Head Neck 2019; 41:3499-3515. [PMID: 31355988 DOI: 10.1002/hed.25866] [Citation(s) in RCA: 41] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2019] [Revised: 06/18/2019] [Accepted: 06/18/2019] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND MicroRNAs (miRNA) recently evolved as potential cancer biomarkers. Therefore, the aim of the present study was to evaluate the prognostic impact of eight miRNAs connected to oral squamous cell carcinoma (OSCC). METHOD Expression levels of hsa-mir-21-5p, hsa-mir-29b-3p, hsa-mir-31-5p, hsa-mir-99a-5p, hsa-mir-99b-3p, hsa-mir-100-5p, hsa-mir-143-3p and hsa-mir-155-5p were analyzed in tumor tissue (n = 36) and healthy oral mucosal tissue (n = 17) and correlated with clinical variables. Results of the study cohort were validated in an OSCC cohort of The Cancer Genome Atlas. RESULTS Increased hsa-mir-99b-3p expression level showed a tendency toward advanced tumor stages, and high levels of hsa-mir-100-5p expression were associated with extracapsular extension. While a high expression level of hsa-mir-99b-3p was associated with better survival, a high expression level of hsa-mir-100-5p was correlated with a poorer survival in the study cohort. CONCLUSION Our results indicate that hsa-mir-99b-3p and hsa-mir-100-5p may serve as novel prognostic biomarkers in OSCC.
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Affiliation(s)
- Mark Jakob
- Department of Otorhinolaryngology, Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany
| | - Lena M Mattes
- Department of Otorhinolaryngology, Universitätsmedizin Göttingen, Georg-August-Universität Göttingen, Göttingen, Germany
| | - Stefan Küffer
- Institute of Pathology, Universitätsmedizin Göttingen, Georg-August-Universität Göttingen, Göttingen, Germany
| | - Kristian Unger
- Clinical Cooperation Group "Personalized Radiotherapy in Head and Neck Cancer", Helmholtz Zentrum München, Research Center for Environmental Health (GmbH), Munich, Germany.,Research Unit Radiation Cytogenetics, Helmholtz Zentrum München, Research Center for Environmental Health (GmbH), Munich, Germany
| | - Julia Hess
- Clinical Cooperation Group "Personalized Radiotherapy in Head and Neck Cancer", Helmholtz Zentrum München, Research Center for Environmental Health (GmbH), Munich, Germany.,Research Unit Radiation Cytogenetics, Helmholtz Zentrum München, Research Center for Environmental Health (GmbH), Munich, Germany
| | - Mattis Bertlich
- Department of Otorhinolaryngology, Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany
| | - Frank Haubner
- Department of Otorhinolaryngology, Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany
| | - Friedrich Ihler
- Department of Otorhinolaryngology, Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany.,German Center for Vertigo and Balance Disorders (DSGZ), Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany
| | - Martin Canis
- Department of Otorhinolaryngology, Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany
| | - Bernhard G Weiss
- Department of Otorhinolaryngology, Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany
| | - Julia Kitz
- Institute of Pathology, Universitätsmedizin Göttingen, Georg-August-Universität Göttingen, Göttingen, Germany.,German Center for Vertigo and Balance Disorders (DSGZ), Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany
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38
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Huang S, Ichikawa Y, Yoshitake K, Kinoshita S, Igarashi Y, Omori F, Maeyama K, Nagai K, Watabe S, Asakawa S. Identification and Characterization of microRNAs and Their Predicted Functions in Biomineralization in the Pearl Oyster ( Pinctada fucata). BIOLOGY 2019; 8:biology8020047. [PMID: 31212990 PMCID: PMC6627748 DOI: 10.3390/biology8020047] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/18/2019] [Revised: 06/12/2019] [Accepted: 06/13/2019] [Indexed: 11/16/2022]
Abstract
The biological process of pearl formation is an ongoing research topic, and a number of genes associated with this process have been identified. However, the involvement of microRNAs (miRNAs) in biomineralization in the pearl oyster, Pinctada fucata, is not well understood. In order to investigate the divergence and function of miRNAs in P. fucata, we performed a transcriptome analysis of small RNA libraries prepared from adductor muscle, gill, ovary, and mantle tissues. We identified 186 known and 42 novel miRNAs in these tissues. Clustering analysis showed that the expression patterns of miRNAs were similar among the somatic tissues, but they differed significantly between the somatic and ovary tissues. To validate the existence of the identified miRNAs, nine known and three novel miRNAs were verified by stem-loop qRT-PCR using U6 snRNA as an internal reference. The expression abundance and target prediction between miRNAs and biomineralization-related genes indicated that miR-1990c-3p, miR-876, miR-9a-3p, and novel-3 may be key factors in the regulatory network that act by controlling the formation of matrix proteins or the differentiation of mineralogenic cells during shell formation in mantle tissue. Our findings serve to further clarify the processes underlying biomineralization in P. fucata.
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Affiliation(s)
- Songqian Huang
- Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan.
| | - Yuki Ichikawa
- Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan.
| | - Kazutoshi Yoshitake
- Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan.
| | - Shigeharu Kinoshita
- Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan.
| | - Yoji Igarashi
- Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan.
| | - Fumito Omori
- Mikimoto Pharmaceutical CO., LTD., Kurose 1425, Ise, Mie 516-8581, Japan.
| | - Kaoru Maeyama
- Mikimoto Pharmaceutical CO., LTD., Kurose 1425, Ise, Mie 516-8581, Japan.
| | - Kiyohito Nagai
- Pearl Research Laboratory, K. MIKIMOTO & CO., LTD., Osaki Hazako 923, Hamajima, Shima, Mie 517-0403, Japan.
| | - Shugo Watabe
- School of Marine Biosciences, Kitasato University, Minami-ku, Sagamihara, Kanagawa 252-0313, Japan.
| | - Shuichi Asakawa
- Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan.
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Zhang L, Meng X, Zhu XW, Yang DC, Chen R, Jiang Y, Xu T. Long non-coding RNAs in Oral squamous cell carcinoma: biologic function, mechanisms and clinical implications. Mol Cancer 2019; 18:102. [PMID: 31133028 PMCID: PMC6535863 DOI: 10.1186/s12943-019-1021-3] [Citation(s) in RCA: 114] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2019] [Accepted: 04/22/2019] [Indexed: 01/17/2023] Open
Abstract
There is growing evidence that regions of the genome that cannot encode proteins play an important role in diseases. These regions are usually transcribed into long non-coding RNAs (lncRNAs). LncRNAs, little or no coding potential, are defined as capped transcripts longer than 200 nucleotides. New sequencing technologies have shown that a large number of aberrantly expressed lncRNAs are associated with multiple cancer types and indicated they have emerged as an important class of pervasive genes during the development and progression of cancer. However, the underlying mechanism in cancer is still unknown. Therefore, it is necessary to elucidate the lncRNA function. Notably, many lncRNAs dysregulation are associated with Oral squamous cell carcinoma (OSCC) and affect various aspects of cellular homeostasis, including proliferation, survival, migration or genomic stability. This review expounds the up- or down-regulation of lncRNAs in OSCC and the molecular mechanisms by which lncRNAs perform their function in the malignant cell. Finally, the potential of lncRNAs as non-invasive biomarkers for OSCC diagnosis are also described. LncRNAs hold promise as prospective novel therapeutic targets, but more research is needed to gain a better understanding of their biologic function.
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Affiliation(s)
- Lei Zhang
- College & Hospital of Stomatology, Anhui Medical University, Key Lab. of Oral Diseases Research of Anhui Province, Hefei, 230032, China.,Department of Periodontology, College and Hospital of Stomatology, Anhui Medical University, Hefei, 230032, Anhui Province, China
| | - Xiang Meng
- School of Stomatology, Anhui Medical University, Hefei, 230032, Anhui Province, China
| | - Xin-Wei Zhu
- College & Hospital of Stomatology, Anhui Medical University, Key Lab. of Oral Diseases Research of Anhui Province, Hefei, 230032, China.,Outpatient Department of Binhu District, College and Hospital of Stomatology, Anhui Medical University, Hefei, 230601, Anhui Province, China
| | - Deng-Cheng Yang
- School of Stomatology, Anhui Medical University, Hefei, 230032, Anhui Province, China
| | - Ran Chen
- School of Stomatology, Anhui Medical University, Hefei, 230032, Anhui Province, China
| | - Yong Jiang
- Department of Stomatology, The Fourth Affiliated Hospital of Anhui Medical University, 372 Tunxi Road, Hefei, 230000, Anhui Province, China.
| | - Tao Xu
- School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, 81 Meishan Road, Hefei, 230032, Anhui Province, China. .,Institute for Liver Diseases of Anhui Medical University, Anhui Medical University, 81 Meishan Road, Hefei, 230032, Anhui Province, China.
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40
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Shams R, Geranpayeh L, Omrani MD, Ghafouri-Fard S. Expression analysis of Inhibitor Of DNA Binding 1 (ID-1) gene in breast cancer. Hum Antibodies 2019; 27:129-134. [PMID: 30856107 DOI: 10.3233/hab-180358] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
BACKGROUND ID-1 gene codes for a helix-loop-helix (HLH) protein that inhibits the DNA binding and transcriptional activation function of these proteins. METHODS We analyzed ID-1 expression in microarray and RNA Sequencing databases as well as 61 breast cancer tissues compared with adjacent non-cancerous tissues (ANCTs). RESULTS Expression analysis of ID-1 gene in two microarray datasets and RNA sequencing data showed down-regulation of ID-1 in tumoral tissues compared with normal tissues. However, ID-1 expression analysis in tumoral tissues and ANCTs obtained from 61 patients revealed its over-expression in tumoral tissues. A negative association was detected between ID-1 expression levels and ER status. CONCLUSION ID-1 expression may be implicated in the pathogenesis of breast cancer especially in patient with ER negative status.
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Affiliation(s)
- Roshanak Shams
- Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Lobat Geranpayeh
- Department of Surgery, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Mir Davood Omrani
- Urogenital Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Soudeh Ghafouri-Fard
- Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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41
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Zhang H, Wang J, Wang Z, Ruan C, Wang L, Guo H. Serum miR-100 is a potential biomarker for detection and outcome prediction of glioblastoma patients. Cancer Biomark 2019; 24:43-49. [PMID: 30530966 DOI: 10.3233/cbm-181416] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- Huiping Zhang
- Department of Neurology, Baoji Hi-Tech People’s Hospital, Baoji, Shaanxi 721000, China
| | - Jianfeng Wang
- Department of Neurology, Shaanxi Nuclear Industry 215 Hospital, Xianyang, Shaanxi 712000, China
| | - Zhanying Wang
- Department of Neurology, Xianyang Hospital of Yan’an University, Xianyang, Shaanxi 712000, China
| | - Cailian Ruan
- Medical College, Yan’an University, Yan’an, Shaanxi 716000, China
| | - Lu Wang
- Medical College, Yan’an University, Yan’an, Shaanxi 716000, China
| | - Hongtao Guo
- College of Physical Education, Yan’an University, Yan’an, Shaanxi 716000, China
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42
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miR-125b suppresses oral oncogenicity by targeting the anti-oxidative gene PRXL2A. Redox Biol 2019; 22:101140. [PMID: 30785086 PMCID: PMC6383183 DOI: 10.1016/j.redox.2019.101140] [Citation(s) in RCA: 57] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2018] [Revised: 01/22/2019] [Accepted: 02/08/2019] [Indexed: 12/11/2022] Open
Abstract
Oral squamous cell carcinoma (OSCC) is a globally prevalent malignancy. The molecular mechanisms of this cancer are not well understood and acquire elucidation. Peroxiredoxin like 2A (PRXL2A) has been reported to be an antioxidant protein that protects cells from oxidative stress. Our previous study identified an association between PRXL2A upregulation in OSCC and a worse patient prognosis. MicroRNAs (miRNAs) are small non-coding RNAs that are involved in the modulation of biological/pathological properties. The miR-125 family of genes drive pluripotent regulation across a wide variety of cancers. In this study, we identify the oncogenic eligibility of PRXL2A and clarify miR-125b as its upstream regulator. Downregulation of miR-125b can be observed in OSCC tumors. Lower miR-125b expression in tumors results in a worse patient prognosis at the relatively early stage. Reporter assays are able to validate that PRXL2A is a direct target of miR-125b. Exogenous miR-125b expression in OSCC cells results in increased oxidative stress, increased drug sensitivity, and suppressor activity that is paralleled by the knockout of PRXL2A gene. The suppressor activity of miR-125b is able to be rescued by PRXL2A, which suggests the existence of a miR-125b-PRXL2A regulatory axis that is part of OSCC pathogenesis. Nuclear factor-erythroid 2-related factor 2 (NRF2) was found to be a downstream effector of the miR-125b-PRXL2A cascade. As a whole, this study has pinpointed novel clues demonstrating that downregulation of miR-125b suppressor underlies upregulation of PRXL2A in OSCC, and this then protects the affected tumor cells from oxidative stress.
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43
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A microRNA signature for the differential diagnosis of salivary gland tumors. PLoS One 2019; 14:e0210968. [PMID: 30682201 PMCID: PMC6347363 DOI: 10.1371/journal.pone.0210968] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2018] [Accepted: 01/04/2019] [Indexed: 12/15/2022] Open
Abstract
Salivary gland tumors (SGTs) are rare tumors of the head and neck with different clinical behavior. Preoperative diagnosis, based on instrumental and cytologic examinations, is crucial for their correct management. The identification of molecular markers might improve the accuracy of pre-surgical diagnosis helping to plan the proper treatment especially when a definitive diagnosis based only on cytomorphology cannot be achieved. miRNAs appear to be new promising biomarkers in the diagnosis and prognosis of cancer. Studies concerning the useful of miRNA expression in clinical decision-making regarding SGTs remain limited and controversial.The expression of a panel of 798 miRNAs was investigated using Nanostring technology in 14 patients with malignant SGTs (6 mucoepidermoid carcinomas, 4 adenoid cystic carcinomas, 1 acinic cell carcinoma, 1 ductal carcinoma, 1 cystadenocarcinoma and 1 adenocarcinoma) and in 10 patients with benign SGTs (pleomorphic adenomas). The DNA Intelligent Analysis (DIANA)-miRPath v3.0 software was used to determinate the miRNA regulatory roles and to identify the controlled significant Kyoto Encyclopedia of Genes and Genomes (KEGG) molecular pathways. Forty six miRNAs were differentially expressed (False Discovery Rate—FDR<0.05) between malignant and benign SGTs. DIANA miRPath software revealed enriched pathways involved in cancer processes as well as tumorigenesis, cell proliferation, cell growth and survival, tumor suppressor expression, angiogenesis and tumor progression. Interestingly, clustering analysis showed that this signature of 46 miRNAs is able to differentiate the two analyzed groups. We found a correlation between histological diagnosis (benign or malignant) and miRNA expression profile.The molecular signature identified in this study might become an important preoperative diagnostic tool.
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Unger L, Gerber V, Pacholewska A, Leeb T, Jagannathan V. MicroRNA fingerprints in serum and whole blood of sarcoid‐affected horses as potential non‐invasive diagnostic biomarkers. Vet Comp Oncol 2018; 17:107-117. [DOI: 10.1111/vco.12451] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2018] [Revised: 10/02/2018] [Accepted: 10/11/2018] [Indexed: 01/06/2023]
Affiliation(s)
- Lucia Unger
- Swiss Institute of Equine Medicine, Department of Clinical Veterinary Medicine, Vetsuisse FacultyUniversity of Bern, and Agroscope Bern Switzerland
| | - Vinzenz Gerber
- Swiss Institute of Equine Medicine, Department of Clinical Veterinary Medicine, Vetsuisse FacultyUniversity of Bern, and Agroscope Bern Switzerland
| | - Alicja Pacholewska
- Institute of Genetics, Vetsuisse FacultyUniversity of Bern Bern Switzerland
| | - Tosso Leeb
- Institute of Genetics, Vetsuisse FacultyUniversity of Bern Bern Switzerland
| | - Vidhya Jagannathan
- Institute of Genetics, Vetsuisse FacultyUniversity of Bern Bern Switzerland
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Krejcik Z, Belickova M, Hrustincova A, Votavova H, Jonasova A, Cermak J, Dyr JE, Merkerova MD. MicroRNA profiles as predictive markers of response to azacitidine therapy in myelodysplastic syndromes and acute myeloid leukemia. Cancer Biomark 2018; 22:101-110. [PMID: 29630523 DOI: 10.3233/cbm-171029] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND Azacitidine (AZA) is a nucleoside analog used for treatment of myelodysplasia and the prediction of AZA responsiveness is important for the therapy management. METHODS Using microarrays and reverse-transcription quantitative-PCR, we analyzed microRNA (miRNA) expression in bone marrow CD34+ cells of 27 patients with higher-risk myelodysplastic syndromes or acute myeloid leukemia with myelodysplasia-related changes before and during AZA treatment. RESULTS At baseline, we found that future overall response rate was significantly higher in patients with upregulated miR-17-3p and downregulated miR-100-5p and miR-133b. Importantly, the high level of miR-100-5p at baseline was associated with shorter overall survival (HR = 4.066, P= 0.008). After AZA treatment, we observed deregulation of 30 miRNAs in responders (including downregulation of miR-10b-5p, miR-15a-5p/b-5p, miR-24-3p, and miR-148b-3p), while their levels remained unchanged in non-responders. CONCLUSIONS Our study demonstrates that responders and non-responders have distinct miRNA patterns and that the level of specific miRNAs before therapy may predict the efficacy of AZA treatment.
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Affiliation(s)
- Zdenek Krejcik
- Institute of Hematology and Blood Transfusion, Prague, Czech Republic
| | - Monika Belickova
- Institute of Hematology and Blood Transfusion, Prague, Czech Republic
| | | | - Hana Votavova
- Institute of Hematology and Blood Transfusion, Prague, Czech Republic
| | | | - Jaroslav Cermak
- Institute of Hematology and Blood Transfusion, Prague, Czech Republic
| | - Jan E Dyr
- Institute of Hematology and Blood Transfusion, Prague, Czech Republic
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Pettit C, Webb A, Walston S, Chatterjee M, Chen W, Frankel W, Croce C, Williams TM. MicroRNA molecular profiling identifies potential signaling pathways conferring resistance to chemoradiation in locally-advanced rectal adenocarcinoma. Oncotarget 2018; 9:28951-28964. [PMID: 29988972 PMCID: PMC6034754 DOI: 10.18632/oncotarget.25652] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2018] [Accepted: 04/02/2018] [Indexed: 12/16/2022] Open
Abstract
Purpose There has been growing interest in using chemoradiation (CRT) for non-operative management of rectal cancer, and identifying patients who might benefit most from this approach is crucial. This study identified miRNAs (miRs) associated with clinical outcomes and treatment resistance by evaluating both pre- and post-CRT expression profiles. Methods Forty patients, 9 with pathologic complete response (pCR) and 31 with pathologic incomplete response (pIR) were included. MicroRNA was extracted from 40 pre-therapy tumor samples and 31 post-chemoradiation surgical samples with pathologic incomplete response (pIR). A generalized linear model was used to identify miRs associated with pCR. A linear mixed effects model was used to identify miRs differentially expressed before and after treatment. miR expression was dichotomized at the mean and clinical outcomes were evaluated using Cox proportional hazard modeling. Results Nine miRs were associated with pCR (p<0.05), but none were significant after false discovery rate correction. Among patients with pIR, 68 miRs were differentially expressed between the pre and post-CRT groups (FDR p<0.05). Ingenuity pathway analysis (IPA) demonstrated multiple signaling networks associated with pIR, including p38MAPK, TP53, AKT, IL-6, and RAS. Increased let-7b was correlated with increased distant metastasis (DM), worse relapse-free survival (RFS), and worse overall survival (OS) (p<0.05). Conclusions No miRs were significantly correlated with pCR. We identified miRs that were differentially expressed between pre- and post-CRT tumor samples, and these miRs implicated multiple signaling pathways that may confer resistance to CRT. In addition, we identified an association between increased let-7b and worse clinical outcomes (DM, DFS, OS).
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Affiliation(s)
- Cory Pettit
- The Ohio State University Medical Center, Arthur G. James Comprehensive Cancer Center and Richard J. Solove Research Institute, Columbus, OH 43210, USA
| | - Amy Webb
- The Ohio State University Medical Center, Arthur G. James Comprehensive Cancer Center and Richard J. Solove Research Institute, Columbus, OH 43210, USA
| | - Steve Walston
- The Ohio State University Medical Center, Arthur G. James Comprehensive Cancer Center and Richard J. Solove Research Institute, Columbus, OH 43210, USA
| | - Moumita Chatterjee
- The Ohio State University Medical Center, Arthur G. James Comprehensive Cancer Center and Richard J. Solove Research Institute, Columbus, OH 43210, USA
| | - Wei Chen
- The Ohio State University Medical Center, Arthur G. James Comprehensive Cancer Center and Richard J. Solove Research Institute, Columbus, OH 43210, USA
| | - Wendy Frankel
- The Ohio State University Medical Center, Arthur G. James Comprehensive Cancer Center and Richard J. Solove Research Institute, Columbus, OH 43210, USA
| | - Carlo Croce
- The Ohio State University Medical Center, Arthur G. James Comprehensive Cancer Center and Richard J. Solove Research Institute, Columbus, OH 43210, USA
| | - Terence M Williams
- The Ohio State University Medical Center, Arthur G. James Comprehensive Cancer Center and Richard J. Solove Research Institute, Columbus, OH 43210, USA
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González-Arriagada WA, Olivero P, Rodríguez B, Lozano-Burgos C, de Oliveira CE, Coletta RD. Clinicopathological significance of miR-26, miR-107, miR-125b, and miR-203 in head and neck carcinomas. Oral Dis 2018; 24:930-939. [PMID: 29667275 DOI: 10.1111/odi.12872] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2018] [Revised: 03/27/2018] [Accepted: 04/10/2018] [Indexed: 12/19/2022]
Abstract
OBJECTIVES MicroRNAs play a role in the development and progression of head and neck squamous cell carcinomas (HNSCC). Our aim was to study the expression of miR-26, miR-107, miR-125b, and miR-203 in primary HNSCC with and without lymph node metastasis and their clinicopathological significance. MATERIALS AND METHODS The expression of microRNAs in primary HNSCC with lymph node metastasis (n = 16) and their matched lymph node, as well as primary tumors without metastasis (n = 16), were determined by quantitative RT-PCR and analyzed with clinicopathological features and survival. RESULTS The expression levels of miR-26 (p < .05) and miR-125b (p < .01) were higher in metastatic primary HNSCC, while levels of miR-203 (p < .01) were lower. The expression of the microRNAs was associated with clinicopathological features, including miR-26 high expression and N stage (p = .04), poor differentiation (p = .005) and recurrence (p = .007), miR-125b high expression and N stage (p = .0005) and death (p = .02), and low levels of miR-203 and N stage (p = .04). The high expression of miR-26 was associated with shortened disease-free survival, and high miR-125b expression was an independent risk factor for poor disease-specific survival. CONCLUSIONS These findings suggest that miR-26 and miR-125b may be associated with the progression and metastasis of HNSCC and that miR-203 is associated with a more favorable prognosis.
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Affiliation(s)
- W A González-Arriagada
- Facultad de Odontología, Patología y Diagnóstico Oral, Universidad de Valparaíso, Valparaíso, Chile
| | - P Olivero
- Facultad de Medicina, Universidad de Valparaíso, Valparaíso, Chile
| | - B Rodríguez
- Facultad de Medicina, Universidad de Valparaíso, Valparaíso, Chile
| | - C Lozano-Burgos
- Servicio de Anatomía Patológica, Hospital Carlos Van Buren, Valparaíso, Chile
| | - C E de Oliveira
- Department Pathology and Parasitology, Institute of Biomedical Sciences, Federal University of Alfenas, Alfenas, Minas Gerais, Brazil.,Oral Pathology, Piracicaba Dental School, University of Campinas, Piracicaba, Brazil
| | - R D Coletta
- Oral Pathology, Piracicaba Dental School, University of Campinas, Piracicaba, Brazil
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Yap T, Koo K, Cheng L, Vella LJ, Hill AF, Reynolds E, Nastri A, Cirillo N, Seers C, McCullough M. Predicting the Presence of Oral Squamous Cell Carcinoma Using Commonly Dysregulated MicroRNA in Oral Swirls. Cancer Prev Res (Phila) 2018; 11:491-502. [PMID: 29764807 DOI: 10.1158/1940-6207.capr-17-0409] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2017] [Revised: 03/02/2018] [Accepted: 05/01/2018] [Indexed: 11/16/2022]
Abstract
Oral swirls are a noninvasive, rapidly collected source of salivary microRNA (miRNA) potentially useful in the early detection of disease states, particularly oral squamous cell carcinoma (OSCC). The aim of this study was to predict the presence of OSCC using a panel of OSCC-related dysregulated miRNA found in oral swirls, identified jointly in data from formalin-fixed paraffin-embedded (FFPE) and fresh-frozen specimens. Next-generation sequencing (NGS) was used to determine miRNA fold changes in FFPE OSCC specimens relative to histologically normal epithelium. These data were placed with NGS of fresh-frozen tissue data of The Cancer Genome Atlas database to select a panel of commonly dysregulated miRNA. This panel was then analyzed by RT-qPCR in RNA extracted from oral swirls collected from 30 patients with OSCC and 30 controls. Upregulation of miR-31 and miR-21 and downregulation of miR-99a, let-7c, miR-125b, and miR-100 were found between OSCC and controls in both FFPE and fresh-frozen samples. These miRNAs were studied in a training set of 15 OSCC versus 15 control oral swirls to develop a dysregulation score [AUC, 0.95; 95% confidence interval (CI), 0.88-1.03] and classification tree. A test cohort of 15 OSCC versus 15 control oral swirls yielded a dysregulation score AUC of 0.86 (95% CI, 0.79-1.00) with the classification tree identifying 100% (15/15) of OSCC and 67% (10/15) of controls. This study debuts the use of OSCC-associated miRNA, commonly dysregulated in both FFPE and frozen specimens, in oral swirls to indicate the presence of OSCC with high accuracy. Cancer Prev Res; 11(8); 491-502. ©2018 AACR.
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Affiliation(s)
- Tami Yap
- Melbourne Dental School, University of Melbourne, Victoria, Australia.
| | - Kendrick Koo
- Department of Surgery, Royal Melbourne Hospital, Victoria, Australia
| | - Lesley Cheng
- Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Victoria, Australia
| | - Laura J Vella
- The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia
| | - Andrew F Hill
- Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Victoria, Australia
| | - Eric Reynolds
- Melbourne Dental School, University of Melbourne, Victoria, Australia.,Oral Health Cooperative Research Centre, Melbourne, Victoria, Australia
| | - Alf Nastri
- Department of Oral and Maxillofacial Surgery, Royal Melbourne Hospital, Victoria, Australia
| | - Nicola Cirillo
- Melbourne Dental School, University of Melbourne, Victoria, Australia.,Oral Health Cooperative Research Centre, Melbourne, Victoria, Australia
| | - Christine Seers
- Melbourne Dental School, University of Melbourne, Victoria, Australia.,Oral Health Cooperative Research Centre, Melbourne, Victoria, Australia
| | - Michael McCullough
- Melbourne Dental School, University of Melbourne, Victoria, Australia.,Oral Health Cooperative Research Centre, Melbourne, Victoria, Australia
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Sun X, Liu X, Wang Y, Yang S, Chen Y, Yuan T. miR-100 inhibits the migration and invasion of nasopharyngeal carcinoma by targeting IGF1R. Oncol Lett 2018; 15:8333-8338. [PMID: 29805566 PMCID: PMC5950178 DOI: 10.3892/ol.2018.8420] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2017] [Accepted: 03/12/2018] [Indexed: 12/26/2022] Open
Abstract
Nasopharyngeal carcinoma (NPC) is a cancer pattern that often develops in the epithelial cells of the nasopharynx. miR-100 is a miRNA that has been identified in a number of cancers. The aim of the present study was to investigate whether miR-100 can affect cell migration and proliferation of NPC by targeting insulin-like growth factor 1 receptor (IGF1R). Western blot analysis was used to determine the protein levels of genes. The reverse transcription-quantitative PCR (RT-qPCR) was used to detect the expression level of miR-100 and IGF1R. Transwell assay was used to detect the migration and invasion of cell lines. The luciferase reporter assay was employed to confirm the target gene of miR-100. miR-100 expression was highly reduced in NPC tissues compared with non-cancerous tissues. Overexpression of miR-100 significantly inhibited the migration and invasion of NPC cell lines C666-1 and SUNE1. IGF1R was a downstream target of miR-100 and was downregulated by miR-100. Knockdown of IGF1R by siRNA suppressed cell proliferation of the C666-1 cell line. The newly identified miR-100/IGF1R axis offers novel biomarkers for the therapeutic intervention of NPC treatment. As a result, our findings suggest that miR-100 plays an important role in suppressing migration and invasion of NPC cells and suppresses IGF1R expression by directly targeting its 3'-UTR. It is suggested that miR-100 may be a novel therapeutic target of microRNA-mediated suppression of cell migration and invasion in NPC. However, the role of the miR-100/IGF1R axis in NPC progression needs further investigation.
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Affiliation(s)
- Xiaoyan Sun
- Department of Otorhinolaryngology, Weifang People's Hospital, Weifang, Shandong 261041, P.R. China
| | - Xiaoying Liu
- Department of Otorhinolaryngology, Weifang People's Hospital, Weifang, Shandong 261041, P.R. China
| | - Yanmei Wang
- Department of Otorhinolaryngology, Weifang People's Hospital, Weifang, Shandong 261041, P.R. China
| | - Shuqin Yang
- Department of Otorhinolaryngology, Weifang People's Hospital, Weifang, Shandong 261041, P.R. China
| | - Yao Chen
- Department of Otorhinolaryngology, Weifang People's Hospital, Weifang, Shandong 261041, P.R. China
| | - Tiejun Yuan
- Department of Otorhinolaryngology, Weifang People's Hospital, Weifang, Shandong 261041, P.R. China
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Daniel SG, Russ AD, Guthridge KM, Raina AI, Estes PS, Parsons LM, Richardson HE, Schroeder JA, Zarnescu DC. miR-9a mediates the role of Lethal giant larvae as an epithelial growth inhibitor in Drosophila. Biol Open 2018; 7:bio.027391. [PMID: 29361610 PMCID: PMC5829493 DOI: 10.1242/bio.027391] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Drosophila lethal giant larvae (lgl) encodes a conserved tumor suppressor with established roles in cell polarity, asymmetric division, and proliferation control. Lgl's human orthologs, HUGL1 and HUGL2, are altered in human cancers, however, its mechanistic role as a tumor suppressor remains poorly understood. Based on a previously established connection between Lgl and Fragile X protein (FMRP), a miRNA-associated translational regulator, we hypothesized that Lgl may exert its role as a tumor suppressor by interacting with the miRNA pathway. Consistent with this model, we found that lgl is a dominant modifier of Argonaute1 overexpression in the eye neuroepithelium. Using microarray profiling we identified a core set of ten miRNAs that are altered throughout tumorigenesis in Drosophila lgl mutants. Among these are several miRNAs previously linked to human cancers including miR-9a, which we found to be downregulated in lgl neuroepithelial tissues. To determine whether miR-9a can act as an effector of Lgl in vivo, we overexpressed it in the context of lgl knock-down by RNAi and found it able to reduce the overgrowth phenotype caused by Lgl loss in epithelia. Furthermore, cross-comparisons between miRNA and mRNA profiling in lgl mutant tissues and human breast cancer cells identified thrombospondin (tsp) as a common factor altered in both fly and human breast cancer tumorigenesis models. Our work provides the first evidence of a functional connection between Lgl and the miRNA pathway, demonstrates that miR-9a mediates Lgl's role in restricting epithelial proliferation, and provides novel insights into pathways controlled by Lgl during tumor progression. Summary: Mir-9a overexpression can suppress the overgrowth phenotype caused by Lgl knock-down in epithelia. Gene profiling identifies pathways dysregulated in lgl mutants and shared features between flies and human cancer cells.
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Affiliation(s)
- Scott G Daniel
- Department of Molecular and Cellular Biology, University of Arizona, Tucson, AZ 85721, USA
| | - Atlantis D Russ
- Department of Molecular and Cellular Biology, University of Arizona, Tucson, AZ 85721, USA.,Genetics Graduate Interdisciplinary Program, University of Arizona, Tucson, AZ 85721, USA.,Arizona Cancer Center, University of Arizona, Tucson, AZ 85721, USA
| | - Kathryn M Guthridge
- Cell Cycle and Development Laboratory, Research Division, Peter MacCallum Cancer Center, Melbourne, Victoria 3000, Australia
| | - Ammad I Raina
- Department of Molecular and Cellular Biology, University of Arizona, Tucson, AZ 85721, USA
| | - Patricia S Estes
- Department of Molecular and Cellular Biology, University of Arizona, Tucson, AZ 85721, USA
| | - Linda M Parsons
- Cell Cycle and Development Laboratory, Research Division, Peter MacCallum Cancer Center, Melbourne, Victoria 3000, Australia.,Department of Genetics, University of Melbourne, Melbourne, Victoria 3010, Australia
| | - Helena E Richardson
- Cell Cycle and Development Laboratory, Research Division, Peter MacCallum Cancer Center, Melbourne, Victoria 3000, Australia.,Sir Peter MacCallum Department of Oncology, Department of Anatomy & Neuroscience, Department of Biochemistry & Molecular Biology, University of Melbourne, Melbourne, Victoria 3000, Australia.,Department of Biochemistry & Genetics, La Trobe Institute of Molecular Science, La Trobe University, Melbourne, Victoria 3086, Australia
| | - Joyce A Schroeder
- Department of Molecular and Cellular Biology, University of Arizona, Tucson, AZ 85721, USA.,Genetics Graduate Interdisciplinary Program, University of Arizona, Tucson, AZ 85721, USA.,Arizona Cancer Center, University of Arizona, Tucson, AZ 85721, USA
| | - Daniela C Zarnescu
- Department of Molecular and Cellular Biology, University of Arizona, Tucson, AZ 85721, USA .,Genetics Graduate Interdisciplinary Program, University of Arizona, Tucson, AZ 85721, USA.,Arizona Cancer Center, University of Arizona, Tucson, AZ 85721, USA
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