Open Access

ARTICLE

miR-125b reverses cisplatin resistance by regulating autophagy via targeting RORA/BNIP3L axis in lung adenocarcinoma

by LEI LIU¹, NA GUO¹, XIANGLING LI², QIAN XU², RUILONG HE³, LIMIN CHENG⁴, CHUNYAN DANG³, XINYU BAI³, YIYING BAI³, XIN WANG³, QIANHUI CHEN³, LI ZHANG^3,*

1 Department of Immunology, Chengde Medical University, Chengde, 067000, China
2 Department of Pathology, Chengde Medical University, Chengde, 067000, China
3 Department of Oncology, The Affiliated Hospital of Chengde Medical University, Chengde, 067000, China
4 Department of Hepatobiliary Surgery, The Affiliated Hospital of Chengde Medical University, Chengde, 067000, China

* Corresponding Author: LI ZHANG. Email:

(This article belongs to the Special Issue: Non-coding RNAs on the Clinical Application of Solid Cancers)

Oncology Research 2024, 32(4), 643-658. https://doi.org/10.32604/or.2023.044491

Received 30 June 2023; Accepted 27 September 2023; Issue published 20 March 2024

Abstract

The platinum-based chemotherapy is one of the most frequently used treatment protocols for lung adenocarcinoma (LUAD), and chemoresistance, however, usually results in treatment failure and limits its application in the clinic. It has been shown that microRNAs (miRNAs) play a significant role in tumor chemoresistance. In this study, miR-125b was identified as a specific cisplatin (DDP)-resistant gene in LUAD, as indicated by the bioinformatics analysis and the real-time quantitative PCR assay. The decreased serum level of miR-125b in LUAD patients was correlated with the poor treatment response rate and short survival time. MiR-125b decreased the A549/DDP proliferation, and the multiple drug resistance- and autophagy-related protein expression levels, which were all reversed by the inhibition of miR-125b. In addition, xenografts of human tumors in nude mice were suppressed by miR-125b, demonstrating that through autophagy regulation, miR-125b could reverse the DDP resistance in LUAD cells, both in vitro and in vivo. Further mechanistic studies indicated that miR-125b directly repressed the expression levels of RORA and its downstream BNIP3L, which in turn inhibited autophagy and reversed chemoresistance. Based on these findings, miR-125b in combination with DDP might be an effective treatment option to overcome DDP resistance in LUAD.

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