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MicroRNA-708 Suppresses Cell Proliferation and Enhances Chemosensitivity of Cervical Cancer Cells to cDDP by Negatively Targeting Timeless
PURPOSE: Cervical cancer is the fourth most common cause of cancer-associated mortality in women worldwide. Previous studies have reported that microRNAs (miRNAs) are involved in multiple biological aspects of cancer progression by regulating gene expression. Here, we investigated the role of microR...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6966141/ https://www.ncbi.nlm.nih.gov/pubmed/32021269 http://dx.doi.org/10.2147/OTT.S227015 |
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author | Zou, Xinwei Zhu, Chenjie Zhang, Lin Zhang, Yi Fu, Fengqing Chen, Youguo Zhou, Jinhua |
author_facet | Zou, Xinwei Zhu, Chenjie Zhang, Lin Zhang, Yi Fu, Fengqing Chen, Youguo Zhou, Jinhua |
author_sort | Zou, Xinwei |
collection | PubMed |
description | PURPOSE: Cervical cancer is the fourth most common cause of cancer-associated mortality in women worldwide. Previous studies have reported that microRNAs (miRNAs) are involved in multiple biological aspects of cancer progression by regulating gene expression. Here, we investigated the role of microRNA-708 (miR-708) in cervical cancer. METHODS: The expression levels of miR-708 in cervical cancer tissues and paired-normal cervical tissues were tested by quantitative polymerase chain reaction (qPCR). The interaction between miR-708 and Timeless was identified by bioinformatics method, dual-luciferase reporter assay, and Western blotting. The effects of over-expression of miR-708 on cell proliferation and cisplatin sensitivity were determined by Cell Counting Kit-8 (CCK-8) and colony formation assay. Cell cycle and apoptosis were analyzed by flow cytometry. DNA damage induced by over-expression of miR-708 was determined by comet assay. Expression levels of the genes involved in repair of DNA damage were analyzed by Western blotting. RESULTS: MiR-708 was down-regulated in cervical cancer tissues compared with paired-normal cervical tissues. By bioinformatics method, Western blotting, and dual-luciferase reporter assay, we found that Timeless was a direct target of miR-708. Furthermore, miR-708 suppressed cellular viability, colony formation, promoted apoptosis, and induced DNA damage levels. MiR-708 also enhanced chemosensitivity of cervical cancer cells to cDDP via impairing the ATR/CHK1 signaling pathway. CONCLUSION: We conclude that miR-708 suppresses cell proliferation, facilitates cisplatin efficacy, and impairs DNA repair pathway in cervical cancer cells. These results demonstrate that miR-708 might be a candidate therapeutic target for future cervical cancer therapy. |
format | Online Article Text |
id | pubmed-6966141 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-69661412020-02-04 MicroRNA-708 Suppresses Cell Proliferation and Enhances Chemosensitivity of Cervical Cancer Cells to cDDP by Negatively Targeting Timeless Zou, Xinwei Zhu, Chenjie Zhang, Lin Zhang, Yi Fu, Fengqing Chen, Youguo Zhou, Jinhua Onco Targets Ther Original Research PURPOSE: Cervical cancer is the fourth most common cause of cancer-associated mortality in women worldwide. Previous studies have reported that microRNAs (miRNAs) are involved in multiple biological aspects of cancer progression by regulating gene expression. Here, we investigated the role of microRNA-708 (miR-708) in cervical cancer. METHODS: The expression levels of miR-708 in cervical cancer tissues and paired-normal cervical tissues were tested by quantitative polymerase chain reaction (qPCR). The interaction between miR-708 and Timeless was identified by bioinformatics method, dual-luciferase reporter assay, and Western blotting. The effects of over-expression of miR-708 on cell proliferation and cisplatin sensitivity were determined by Cell Counting Kit-8 (CCK-8) and colony formation assay. Cell cycle and apoptosis were analyzed by flow cytometry. DNA damage induced by over-expression of miR-708 was determined by comet assay. Expression levels of the genes involved in repair of DNA damage were analyzed by Western blotting. RESULTS: MiR-708 was down-regulated in cervical cancer tissues compared with paired-normal cervical tissues. By bioinformatics method, Western blotting, and dual-luciferase reporter assay, we found that Timeless was a direct target of miR-708. Furthermore, miR-708 suppressed cellular viability, colony formation, promoted apoptosis, and induced DNA damage levels. MiR-708 also enhanced chemosensitivity of cervical cancer cells to cDDP via impairing the ATR/CHK1 signaling pathway. CONCLUSION: We conclude that miR-708 suppresses cell proliferation, facilitates cisplatin efficacy, and impairs DNA repair pathway in cervical cancer cells. These results demonstrate that miR-708 might be a candidate therapeutic target for future cervical cancer therapy. Dove 2020-01-09 /pmc/articles/PMC6966141/ /pubmed/32021269 http://dx.doi.org/10.2147/OTT.S227015 Text en © 2020 Zou et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
spellingShingle | Original Research Zou, Xinwei Zhu, Chenjie Zhang, Lin Zhang, Yi Fu, Fengqing Chen, Youguo Zhou, Jinhua MicroRNA-708 Suppresses Cell Proliferation and Enhances Chemosensitivity of Cervical Cancer Cells to cDDP by Negatively Targeting Timeless |
title | MicroRNA-708 Suppresses Cell Proliferation and Enhances Chemosensitivity of Cervical Cancer Cells to cDDP by Negatively Targeting Timeless |
title_full | MicroRNA-708 Suppresses Cell Proliferation and Enhances Chemosensitivity of Cervical Cancer Cells to cDDP by Negatively Targeting Timeless |
title_fullStr | MicroRNA-708 Suppresses Cell Proliferation and Enhances Chemosensitivity of Cervical Cancer Cells to cDDP by Negatively Targeting Timeless |
title_full_unstemmed | MicroRNA-708 Suppresses Cell Proliferation and Enhances Chemosensitivity of Cervical Cancer Cells to cDDP by Negatively Targeting Timeless |
title_short | MicroRNA-708 Suppresses Cell Proliferation and Enhances Chemosensitivity of Cervical Cancer Cells to cDDP by Negatively Targeting Timeless |
title_sort | microrna-708 suppresses cell proliferation and enhances chemosensitivity of cervical cancer cells to cddp by negatively targeting timeless |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6966141/ https://www.ncbi.nlm.nih.gov/pubmed/32021269 http://dx.doi.org/10.2147/OTT.S227015 |
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