Open Access

ARTICLE

LncRNA-POIR knockdown promotes hepatocellular carcinoma sensitivity to sorafenib through upregulating miR-182-5p and inhibiting autophagy

by JIAN XU^1,#, HAILONG GE^1,#, CHEN CHAO¹, FENG MO¹, YU WANG¹, DENGKUI ZHANG¹, XIAOXIAO ZHENG², LI ZHENG², XUEMEI LU², WEI CHEN², QUN XU^1,*, WEIXIN YU^1,*

1 Jintan Affiliated Hospital of Jiangsu University, Changzhou, 213200, China
2 Tongde Hospital of Zhejiang Province, Hangzhou, 310012, China

* Address correspondence to: Weixin Yu, ; Qun Xu,
# Jian Xu and Hailong Ge contributed equally to this work

BIOCELL 2022, 46(6), 1493-1503. https://doi.org/10.32604/biocell.2022.016962

Received 14 April 2021; Accepted 24 August 2021; Issue published 07 February 2022

Abstract

Although sorafenib has been found to prolong the survival time of patients with hepatocellular carcinoma (HCC), sorafenib resistance remains an important challenge. Increasing studies have demonstrated that long noncoding RNAs (lncRNAs) contribute to drug resistance in a wide number of cancers. Human periodontal ligament stem cell (PDLSC) osteogenesis impairment-related lncRNA (POIR) is a recently defined lncRNA for which little is known regarding its function. Our study aimed to reveal the role of POIR in the development of HCC cell sorafenib resistance. The level of POIR expression in patients and tumor cells was examined by Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) assay. CCK-8, EdU, and flow cytometry assay were adopted to examine cell viability, proliferation, and apoptosis, respectively. The autophagy-associated protein expressions were determined by western blotting and autophagic flux analysis. The results of this study exhibited increased POIR in HCC tissues and cells and may be correlated with sorafenib resistance. Knockdown of POIR elevated sorafenib sensitivity by suppressing autophagy in HCC cells. Mechanically, POIR knockdown upregulated miR-182-5p, implying that miR-182-5p mediates POIR regulation. MiR-182-5p overexpression significantly enhanced chemosensitivity to sorafenib, whereas miR-182-5p inhibition had the opposite effect. The sensitization of POIR siRNA to sorafenib was abolished by co-transfection with miR-182-5p inhibitor. Our findings provide a potential target for further clinical treatment of sorafenib-resistant HCC patients.

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