MicroRNA‑29a enhances cisplatin sensitivity in non‑small cell lung cancer through the regulation of REV3L

Chen,Xialin; Zhu,Hong; Ye,Wanli; Cui,Yayun; Chen,Ming

doi:10.3892/mmr.2018.9723

MicroRNA‑29a enhances cisplatin sensitivity in non‑small cell lung cancer through the regulation of REV3L

Authors:
- Xialin Chen
- Hong Zhu
- Wanli Ye
- Yayun Cui
- Ming Chen
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Affiliations: Department of Oncology, The Second Affiliated Hospital of Soochow University, Gusu, Suzhou, Jiangsu 215000, P.R. China, Department of Radiation Oncology, Minhang Branch of Cancer Hospital of Fudan University, Shanghai 200240, P.R. China, Department of Radiation Oncology, The Affiliated Provincial Hospital of Anhui Medical University, Hefei, Anhui 230000, P.R. China, Department of Radiation Oncology, Zhejiang Cancer Hospital, Gongshu, Hangzhou, Zhejiang 310000, P.R. China
Published online on: December 4, 2018 https://doi.org/10.3892/mmr.2018.9723
Pages: 831-840
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Cisplatin‑based chemotherapy may greatly enhance patient prognosis; however, chemotherapy resistance remains an obstacle to curing patients with non‑small cell lung cancer (NSCLC). The aim of the present study was to explore the microRNAs (miRs) that could regulate cisplatin sensitivity and provide a potential treatment method for cisplatin resistance in clinical. Results from the present study revealed that miR‑29a overexpression enhanced and miR‑29a inhibition reduced the sensitivity of two NSCLC cell lines, A549 and H1650, to cisplatin treatment. In addition, reduced miR‑29a expression levels were observed in cisplatin‑resistant A549 cells (A549rCDDP), and increased expression of miR‑29a augmented cisplatin‑induced inhibition of proliferation and apoptosis in A549rCDDP cells. These data indicated that miR‑29a expression may be involved in the development of cisplatin resistance. miR‑29a was revealed to negatively regulate REV3‑like DNA‑directed polymerase ζ catalytic subunit (REV3L) expression in both A549 and H1650 cells; elevated expression of REV3L in A549rCDDP cells was also detected. REV3L encodes the catalytic subunit of DNA polymerase ζ and was hypothesized, based on results from the online tool TargetScan 7.1, to be a target gene of miR‑29a; this was confirmed with a dual luciferase assay. Cells treated with a very low concentration of cisplatin exhibited a significant reduction in proliferation and cell cycle arrest at the G2/M phase in REV3L‑knockdown as well as in miR‑29a‑upregulated A549 cells. Notably, reduced miR‑29a expression and an increase in REV3L mRNA expression were observed in tumor tissues from patients with NSCLC. Additionally, a negative correlation between miR‑29a and REV3L mRNA expression levels in tumor tissues from patients with NSCLC was observed; low expression of miR‑29a and high expression of REV3L were closely associated with an advanced tumor‑node‑metastasis classification. The results of the present study suggested a pivotal role of miR‑29a in mediating NSCLC cell sensitivity towards cisplatin through the regulation of REV3L.

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