Knockdown of lncRNA ANRIL inhibits the development of cisplatin resistance by upregulating miR‑98 in lung cancer cells

Wang,Xi; Zhang,Guojun; Cheng,Zhe; Dai,Lingling; Jia,Liuqun; Jing,Xiaogang; Wang,Huan; Zhang,Rui; Liu,Meng; Jiang,Tianci; Yang,Yuanjian; Yang,Meng

doi:10.3892/or.2020.7685

Knockdown of lncRNA ANRIL inhibits the development of cisplatin resistance by upregulating miR‑98 in lung cancer cells

Authors:
- Xi Wang
- Guojun Zhang
- Zhe Cheng
- Lingling Dai
- Liuqun Jia
- Xiaogang Jing
- Huan Wang
- Rui Zhang
- Meng Liu
- Tianci Jiang
- Yuanjian Yang
- Meng Yang
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Affiliations: Department of Respiration, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
Published online on: July 13, 2020 https://doi.org/10.3892/or.2020.7685
Pages: 1025-1036

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Abstract

Emerging evidence has demonstrated that abnormally expressed long non‑coding (lnc) RNAs contribute to drug resistance in various types of malignancy. LncRNA antisense non‑coding RNA in the inhibitor of cyclin‑dependent kinase 4 locus (ANRIL) exerts oncogenic activity and acts as a key player in a variety of carcinomas, including non‑small cell lung cancer. The present study aimed to investigate the functional roles of ANRIL in cisplatin (DDP) resistance of lung cancer and the underlying mechanism involved in the competing endogenous RNA regulatory network. The expression levels of ANRIL and microRNA (miR)‑98 in lung cancer tissues and DDP‑resistant lung cancer cells were assessed by reverse transcription‑quantitative (RT‑q) PCR. The Pearson's correlation coefficient was used to determine the correlation between the expression levels of ANRIL and miR‑98 in lung cancer tissues. Cell proliferation and apoptosis were detected by MTT assay and flow cytometry analysis, respectively. The expression levels of proliferation‑ and apoptosis‑associated proteins were detected by western blot analysis. The potential interaction between ANRIL and miR‑98 was confirmed by RNA immunoprecipitation (RIP), dual luciferase reporter assay and RT‑qPCR. The results of the present study demonstrated that ANRIL was upregulated and miR‑98 was downregulated in lung cancer tissues and A549/DDP cells. In addition, the Pearson's correlation analysis revealed that the expression of ANRIL was significantly negatively correlated with that of miR‑98 in lung cancer tissues. ANRIL overexpression reversed the DDP‑induced cell proliferation suppression and apoptosis in lung cancer cells, whereas ANRIL knockdown exhibited the opposite effects. RIP, dual luciferase reporter assay and RT‑qPCR analysis results demonstrated that ANRIL directly interacted with miR‑98 and suppressed miR‑98 expression. Furthermore, transfection with the miR‑98 mimics promoted DDP‑induced cell proliferation inhibition and apoptosis in lung cancer cells, and these effects were partially reversed by ANRIL overexpression. In conclusion, ANRIL knockdown inhibited the development of DDP resistance by upregulating miR‑98, providing novel insights into the molecular mechanism of ANRIL involvement in DDP resistance of lung cancer cells.

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