MicroRNA‑29c restores cisplatin sensitivity in liver cancer through direct inhibition of sirtuin 1 expression

Zhang,Wei; Luo,Peng

doi:10.3892/ol.2018.8801

MicroRNA‑29c restores cisplatin sensitivity in liver cancer through direct inhibition of sirtuin 1 expression

Authors:
- Wei Zhang
- Peng Luo
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Affiliations: Department of Geriatric Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, P.R. China, Department of Cardiology, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, P.R. China
Published online on: May 24, 2018 https://doi.org/10.3892/ol.2018.8801
Pages: 1543-1550
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Liver cancer is one of the most prevalent human tumors in the world. Despite recent advances regarding the understanding of the molecular basis of liver cancer and the introduction of novel chemotherapeutic approaches, liver cancer remains associated with a poor prognosis. Sirtuin 1 (SIRT1) was identified to be abnormally upregulated in liver cancer. Dysregulation of microRNAs (miRs/miRNAs) is associated with a variety of types of cancer, and miRNAs may also serve a role in tumorigenesis and progression. The present study demonstrated that following the selection of the cisplatin chemoresistant HepG2 cell line, miR‑29c is downregulated using reverse transcription‑quantitative polymerase chain reaction. Furthermore, overexpression of miR‑29c in cisplatin‑resistant cancer cells was demonstrated to inhibit tumor cell proliferation and to promote apoptosis in vitro and in vivo, as well as restoring cisplatin chemosensitivity by using a cell counting assay, colony formation assay, Annexin V‑fluorescein isothocyanate/propidium iodide apoptosis analysis, terminal deoxynucleotidyl transferase dUTP nick end labeling and xenograft tumors in nude mice. Mechanistically, according to bioinformatics analysis and a luciferase assay, miR‑29c may directly target SIRT1 mRNA and repress SIRT1 expression, which is positively associated with the chemoresistance of liver cancer and may ultimately provide a novel therapeutic method.

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