Long non-coding RNA FGD5-AS1 contributes to cisplatin resistance in hepatocellular carcinoma via sponging microRNA-153-3p by upregulating Twinfilin Actin Binding Protein 1 (TWF1)

Bioengineered. 2021 Dec;12(1):6713-6723. doi: 10.1080/21655979.2021.1971484.

Abstract

Long non-coding RNA (lncRNA) FGD5 antisense RNA 1 (FGD5-AS1) was reported to exert critical roles in multiple cancers. The current work aimed to determine the role of FGD5-AS1 in cisplatin (DDP) resistance of hepatocellular carcinoma (HCC). The levels of FGD5-AS1, miR-153-3p, and twinfilin actin binding protein 1 (TWF1) were analyzed using RT-qPCR. CCK-8, colony formation, Transwell, and TUNEL assays were used to examine the IC50 value of DDP, cell viability, invasion, and apoptosis. The interaction between miR-153-3p and TWF1 or FGD5-AS1 was determined by luciferase reporter and RIP assays. In our study, we found that FGD5-AS1 level was elevated in DDP-resistant HCC tissues and cell lines. FGD5-AS1 silencing improved the sensitivity of HCC cells to DDP. Moreover, FGD5-AS1 directly bound to miR-153-3p and FGD5-AS1 addition neutralized the inhibitory impacts of miR-153-3p supplementation on DDP resistance in the HCC cells. In addition, knockdown of TWF1 inhibited DDP resistance of HCC cells, which was reversed by miR-153-3p deletion. Lastly, FGD5-AS1 interference decreased TWF1 expression level, which was rescued by miR-153-3p inhibition. Our study exhibited that FGD5-AS1 promoted DDP resistance through modulating the miR-153-3p/TWF1 axis in HCC cells. This could be an effective treatment strategy for HCC patients.

Keywords: Hepatocellular carcinoma; cisplatin resistance; fgd5-as1; miR-153-3p; twf1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Hepatocellular* / genetics
  • Carcinoma, Hepatocellular* / metabolism
  • Cisplatin / pharmacology*
  • Drug Resistance, Neoplasm / drug effects
  • Drug Resistance, Neoplasm / genetics
  • Humans
  • Liver Neoplasms* / genetics
  • Liver Neoplasms* / metabolism
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Microfilament Proteins / genetics
  • Microfilament Proteins / metabolism
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / metabolism
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • Up-Regulation / genetics

Substances

  • MIRN153 microRNA, human
  • MicroRNAs
  • Microfilament Proteins
  • RNA, Long Noncoding
  • TWF1 protein, human
  • Protein-Tyrosine Kinases
  • Cisplatin

Grants and funding

This study was supported by 2019 high-level health talents ‘Six first Project’ scientific research project (LGY2019022).