LncRNA GASAL1 promotes hepatocellular carcinoma progression by up-regulating USP10-stabilized PCNA

Exp Cell Res. 2022 Jun 1;415(1):112973. doi: 10.1016/j.yexcr.2021.112973. Epub 2021 Dec 14.

Abstract

Hepatocellular carcinoma (HCC) is a fatal malignancy which has insufficient treatment options. Long non-coding RNA (lncRNA) GASAL1 was discovered to be conspicuously up-regulated in HCC. However, the study on the role of GASAL1 in HCC reamins limited. Our study aimed at exploring the role and mechanism of GASAL1 in HCC. RT-qPCR or Western blot was conducted to examine the expression of RNAs or proteins. Functional assays were carried out to investigate the impact of GASAL1, USP10, and PCNA on HCC cells. Mechanism assays were performed to fathom out the relationship among GASAL1, miR-193b-5p, USP10, and PCNA. In vivo assays were also employed to determine the role of GASAL1 in HCC tumor growth and metastases. According to the data collected, GASAL1 displayed a high expression in HCC cells and GASAL1 knockdown led to impeded cell proliferation and migration, as well as tumor progression. A series of mechanism analysis demonstrated GASAL1 could sponge miR-193b-5p to raise the expression of USP10. Moreover, USP10 could induce PCNA deubiquitination to promote HCC cell growth. To conclude, GASAL1 plays an oncogenic role in HCC. GASAL1 could up-regulate USP10 via competitively binding to miR-193b-5p. And USP10 could strengthen cell proliferative and migratory abilities through deubiquitinating PCNA.

Keywords: Deubiquitination; Hepatocellular carcinoma; PCNA; USP10; lncRNA GASAL1.

MeSH terms

  • Carcinoma, Hepatocellular* / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Liver Neoplasms* / pathology
  • MicroRNAs* / metabolism
  • Proliferating Cell Nuclear Antigen / genetics
  • Proliferating Cell Nuclear Antigen / metabolism
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • Ubiquitin Thiolesterase / genetics
  • Ubiquitin Thiolesterase / metabolism

Substances

  • MicroRNAs
  • Proliferating Cell Nuclear Antigen
  • RNA, Long Noncoding
  • USP10 protein, human
  • Ubiquitin Thiolesterase