Circ_0091579 enhances the malignancy of hepatocellular carcinoma via miR-1287/PDK2 axis

Junwei Shu; Jiayuan Du; Futao Wang; Yong Cheng; Gangxin Chen; Bing Xu; Dianpeng Zhang; Shuangjiang Chen

doi:10.1515/biol-2021-0009

Circ_0091579 enhances the malignancy of hepatocellular carcinoma via miR-1287/PDK2 axis

Open Life Sci. 2021 Jan 25;16(1):69-83. doi: 10.1515/biol-2021-0009. eCollection 2021.

Authors

Junwei Shu¹, Jiayuan Du¹, Futao Wang¹, Yong Cheng¹, Gangxin Chen¹, Bing Xu¹, Dianpeng Zhang¹, Shuangjiang Chen¹

Affiliation

¹ Department of General Surgery, Ankang People's Hospital of Shanxi Province, Ankang, 6-1-3302, Shifu Courtyard, High-Tech Zone, Ankang 725000, Shanxi Province, China.

Abstract

Several articles have indicated that circular RNAs are involved in pathogenesis of human cancers. Nevertheless, the role of circ_0091579 in hepatocellular carcinoma (HCC) progression remains to be revealed. Quantitative reverse transcriptase polymerase chain reaction was carried out to examine the expression of circ_0091579 and miR-1287. The proliferation of HCC cells was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Flow cytometry was performed to analyze cell cycle progression and apoptosis. Western blot assay was conducted to detect the protein expression of CyclinD1, Cleaved caspase3, and pyruvate dehydrogenase kinase 2 (PDK2). Cell glycolysis was evaluated by measuring the uptake of glucose, the production of lactate, and extracellular acidification rate. The target relationship between miR-1287 and circ_0091579 or PDK2 was verified by dual-luciferase reporter assay, RNA immunoprecipitation assay, and RNA-pull down assay. The enrichment of circ_0091579 was enhanced in HCC tissues (n = 77) and four HCC cell lines (HB611, Huh-7, MHCC97, and SNU423) compared with adjacent non-tumor tissues (n = 77) and normal human liver cell line THLE-2. Circ_0091579 mediated the promotion of proliferation and glycolysis and the suppression of apoptosis of HCC cells. MiR-1287 was a direct target of circ_0091579 in HCC cells. MiR-1287 knockdown reversed the effects caused by circ_0091579 interference on the functions of HCC cells. PDK2 could bind to miR-1287 in HCC cells. Circ_0091579 upregulated the enrichment of PDK2 by acting as a sponge of miR-1287 in HCC cells. The influence caused by circ_0091579 intervention on HCC cells was attenuated by overexpression of PDK2. Circ_0091579 interference impeded the progression of HCC in vivo. Circ_0091579 deteriorated HCC by promoting the proliferation and glycolytic metabolism and suppressing the apoptosis of HCC cells via miR-1287/PDK2 axis.

Keywords: PDK2; circ_0091579; glycolysis; hepatocellular carcinoma; miR-1287.