Tianjin Medical Journal ›› 2022, Vol. 50 ›› Issue (5): 455-460.doi: 10.11958/20203618

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Study on the mechanism of LncRNA ZFAS1 targeting miR-373 to induce cisplatin resistance in hepatocellular carcinoma cells

YU Kuiyang, LIU Pan, ZHANG Haowen, QIN Tao, HU Mingxing△   

  1. The Fifth Ward of Pancreatic Surgery, Henan Province People's Hospital, Zhengzhou 450003, China
  • Received:2020-12-30 Revised:2021-11-23 Published:2022-05-15 Online:2022-07-04

Abstract: Objective To explore the mechanism of long non-coding RNA (LncRNA) zinc finger antisense 1 (ZFAS1) targeting microRNA (miR)-373 to induce cisplatin (DDP) resistance in hepatoma cells. Methods There were the normal culture group, the si-NC group and the si-ZFAS1 group in this study. The levels of ZFAS1 and miR-373 were detected by real-time quantitative PCR (qPCR). The cells were treated with DDP (0, 50, 100, 200 and 300 μmol/L) for 12 h on the basis of the si-NC group and the si-ZFAS1 group. CCK-8 was used to detect cell proliferation. Transwell was used to detect cell invasion. Western blot assay was used to detect the protein levels of matrix metalloproteinase (MMP)2 and MMP9. Double luciferase was used to verify the targeting relationship between ZFAS1 and miR-373. Inhibitor miR-373 was added on the basis of the si-ZFAS1 group, and the expression levels of MMP2 and MMP9 were detected. Results The expression level of ZFAS1 was lower in the si-ZFAS1 group than that of the normal culture group and the si-NC group, and the expression level of miR-373 was higher than that of the normal culture group and the si-NC group (P<0.05). After treatment with different concentrations of cisplatin, the cell proliferation rate, invasion number and the expression levels of invasion proteins MMP2 and MMP9 basically showed a decreasing trend in the si-NC group and the si-ZFAS1 group. The above indexes were lower in the si-ZFAS1 group than their corresponding concentrations of the si-NC group (P<0.05). Starbase analysis showed that miR-373 and ZFAS1 had complementary binding sites, which were verified by double luciferase. The expression levels of MMP2 and MMP9 proteins were higher in the si-ZFAS1+inhibitor miR-373 group than those in the si-ZFAS1 group and the si-ZFAS1+inhibitor NC group (P<0.05). Conclusion ZFAS1 may reduce DDP resistance in liver cancer cells, and the mechanism may be related to the regulation of miR-373.

Key words: liver neoplasms, cisplatin, drug resistance, neoplasm, RNA, long noncoding, long non-coding RNA zinc finger antisense 1, microRNA-373

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