MicroRNA‑96 expression induced by low‑dose cisplatin or doxorubicin regulates chemosensitivity, cell death and proliferation in gastric cancer SGC7901 cells by targeting FOXO1

Lang,Chunhui; Xu,Miao; Zhao,Ziyi; Chen,Jinyao; Zhang,Lishi

doi:10.3892/ol.2018.9122

MicroRNA‑96 expression induced by low‑dose cisplatin or doxorubicin regulates chemosensitivity, cell death and proliferation in gastric cancer SGC7901 cells by targeting FOXO1

Authors:
- Chunhui Lang
- Miao Xu
- Ziyi Zhao
- Jinyao Chen
- Lishi Zhang
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Affiliations: Department of Nutrition, Food Safety and Toxicology, West China School of Public Health, Sichuan University, Chengdu, Sichuan 610041, P.R. China, Central Laboratory, The Teaching Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 610072, P.R. China
Published online on: July 11, 2018 https://doi.org/10.3892/ol.2018.9122
Pages: 4020-4026

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Abstract

MicroRNA‑96 (miR‑96) is transcriptionally associated with the induction of chemoresistance following chemotherapy by targeting to FOXO1 mRNA at one of two predicted binding sites in its 3'‑untranslated region sequence. The upregulation of miR‑96 is associated with a high risk of chemoresistance. Nevertheless, the mechanism by which miR‑96 is upregulated remains largely undefined. In the present study, the gastric cancer SGC7901 cell line was treated with different doses of the chemotherapeutic agents cisplatin and doxorubicin. miR‑96 expression was analyzed by reverse transcription‑quantitative polymerase chain reaction at different time points. Western blot and chromatin immunoprecipitation were performed to analyze the expression levels of the target gene. The effects of miR‑96 on chemosensitivity were assessed by a carboxyfluorescein succinimidyl ester/propidium iodide labeling assay, and its effects on proliferation were assessed by Cell Counting Kit‑8 or EdU staining assays. The results demonstrated that treatment with a low dose of either chemotherapeutic agent induced miR‑96 expression. Upregulation of miR‑96 caused the post‑transcriptional repression of FOXO1 expression. Decreases in FOXO1 protein levels led to a decrease in the transcriptional activity of the cyclin‑dependent kinase inhibitor 1A (CDKN1A, also known as p21) promoter region, and thus the expression of p21 was downregulated in a tumor protein p53‑independent manner. As a result, induction of miR‑96 expression caused chemoresistance and promoted proliferation in SGC7901 cells. Taken together, the results of the present study revealed that treatment with cisplatin or doxorubicin could induce expression of miR‑96 at certain doses. Upregulation of miR‑96 is partially associated with chemoresistance and miR‑96 can also promote cell proliferation by repressing p21.

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