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Oncogenic role of MiR-130a in oral squamous cell carcinoma
Aberrant activation of the PI3K/AKT/mTOR pathway is attributed to the pathogenesis of oral squamous cell carcinoma (OSCC). In recent years, increasing evidence suggests the involvement of microRNAs (miRNAs) in oral carcinogenesis by acting as tumor suppressors or oncogenes. TSC1, as a component of t...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8032739/ https://www.ncbi.nlm.nih.gov/pubmed/33833339 http://dx.doi.org/10.1038/s41598-021-87388-4 |
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author | Mallela, Karthik Shivananda, Swamy Gopinath, Kodaganur S. Kumar, Arun |
author_facet | Mallela, Karthik Shivananda, Swamy Gopinath, Kodaganur S. Kumar, Arun |
author_sort | Mallela, Karthik |
collection | PubMed |
description | Aberrant activation of the PI3K/AKT/mTOR pathway is attributed to the pathogenesis of oral squamous cell carcinoma (OSCC). In recent years, increasing evidence suggests the involvement of microRNAs (miRNAs) in oral carcinogenesis by acting as tumor suppressors or oncogenes. TSC1, as a component of the above pathway, regulates several cellular functions such as cell proliferation, apoptosis, migration and invasion. Downregulation of TSC1 is reported in oral as well as several other cancers and is associated with an unfavourable clinical outcome in patients. Here we show that oncogenic miR-130a binds to the 3′UTR of TSC1 and represses its expression. MiR-130a-mediated repression of TSC1 increases cell proliferation, anchorage independent growth and invasion of OSCC cells, which is dependent on the presence of the 3′UTR in TSC1. We observe an inverse correlation between the expression levels of miR-130a and TSC1 in OSCC samples, suggesting that their interaction is physiologically relevant. Delivery of antagomiR-130a to OSCC cells results in a significant decrease in xenograft size. Taken together, the findings of the study indicate that miR-130a-mediated TSC1 downregulation is not only a novel mechanism in OSCC, but also the restoration of TSC1 levels by antagomiR-130a may be a potential therapeutic strategy for the treatment of OSCC. |
format | Online Article Text |
id | pubmed-8032739 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-80327392021-04-09 Oncogenic role of MiR-130a in oral squamous cell carcinoma Mallela, Karthik Shivananda, Swamy Gopinath, Kodaganur S. Kumar, Arun Sci Rep Article Aberrant activation of the PI3K/AKT/mTOR pathway is attributed to the pathogenesis of oral squamous cell carcinoma (OSCC). In recent years, increasing evidence suggests the involvement of microRNAs (miRNAs) in oral carcinogenesis by acting as tumor suppressors or oncogenes. TSC1, as a component of the above pathway, regulates several cellular functions such as cell proliferation, apoptosis, migration and invasion. Downregulation of TSC1 is reported in oral as well as several other cancers and is associated with an unfavourable clinical outcome in patients. Here we show that oncogenic miR-130a binds to the 3′UTR of TSC1 and represses its expression. MiR-130a-mediated repression of TSC1 increases cell proliferation, anchorage independent growth and invasion of OSCC cells, which is dependent on the presence of the 3′UTR in TSC1. We observe an inverse correlation between the expression levels of miR-130a and TSC1 in OSCC samples, suggesting that their interaction is physiologically relevant. Delivery of antagomiR-130a to OSCC cells results in a significant decrease in xenograft size. Taken together, the findings of the study indicate that miR-130a-mediated TSC1 downregulation is not only a novel mechanism in OSCC, but also the restoration of TSC1 levels by antagomiR-130a may be a potential therapeutic strategy for the treatment of OSCC. Nature Publishing Group UK 2021-04-08 /pmc/articles/PMC8032739/ /pubmed/33833339 http://dx.doi.org/10.1038/s41598-021-87388-4 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Mallela, Karthik Shivananda, Swamy Gopinath, Kodaganur S. Kumar, Arun Oncogenic role of MiR-130a in oral squamous cell carcinoma |
title | Oncogenic role of MiR-130a in oral squamous cell carcinoma |
title_full | Oncogenic role of MiR-130a in oral squamous cell carcinoma |
title_fullStr | Oncogenic role of MiR-130a in oral squamous cell carcinoma |
title_full_unstemmed | Oncogenic role of MiR-130a in oral squamous cell carcinoma |
title_short | Oncogenic role of MiR-130a in oral squamous cell carcinoma |
title_sort | oncogenic role of mir-130a in oral squamous cell carcinoma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8032739/ https://www.ncbi.nlm.nih.gov/pubmed/33833339 http://dx.doi.org/10.1038/s41598-021-87388-4 |
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