Circular RNA Circ_0008043 promotes the proliferation and metastasis of hepatocellular carcinoma cells by regulating the microRNA (miR)-326/RAB21 axis

Bioengineered. 2022 Mar;13(3):6600-6614. doi: 10.1080/21655979.2022.2044260.

Abstract

Circular RNAs (circRNAs) are non-coding RNAs with covalently closed structures that modulate the progression of hepatocellular carcinoma (HCC). Here, we explored whether circ_0008043 regulated the biological function of HCC cells. Quantitative real-time polymerase chain reaction (qPCR) was used to detect circ_0008043, microRNA (miR)-326, and RAB21 levels. Expression of E-cadherin, N-cadherin, and vimentin was assessed using qPCR. Cell proliferation, migration, and invasion were evaluated using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, colony formation, and transwell assays. Xenograft tumors were used to evaluate cell growth in vivo. The interaction between miR-326 and circ_0008043 or RAB21 was assessed using dual-luciferase reporter analysis and RNA pull-down analysis. The data illustrated that circ_0008043 and RAB21 were highly expressed, while miR-326 was expressed at less levels in HCC tissues and cells. Interfering with circ_0008043 suppressed cellular proliferation, migration, invasion, and cell growth. Circ_0008043 was confirmed to be an miR-326 sponge that targets RAB21. Rescue experiments showed that inhibiting miR-326 abrogated the effect induced by knockdown of circ_0008043, and overexpressed RAB21 abolished the effect induced by miR-326 overexpression. In summary, silencing of circ_0008043 impeded HCC progression by regulating the miR-326/RAB21 axis. These data suggest that circ_0008043 may have clinical value in the treatment of HCC.

Keywords: RAB21; circ_0008043; hepatocellular carcinoma; invasion; miR-326; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Hepatocellular* / genetics
  • Carcinoma, Hepatocellular* / metabolism
  • Carcinoma, Hepatocellular* / pathology
  • Cell Proliferation / genetics
  • Female
  • Humans
  • Liver Neoplasms* / genetics
  • Liver Neoplasms* / metabolism
  • Liver Neoplasms* / pathology
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Metastasis / genetics
  • RNA, Circular / genetics*
  • rab GTP-Binding Proteins / genetics*

Substances

  • MIRN326 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • RAB21 protein, human
  • rab GTP-Binding Proteins

Grants and funding

This work was supported by Shenzhen Key Medical Discipline Construction Fund under Grant number SZXK079; Youth Fund of The Third People’s Hospital of Shenzhen under Grant number G2021003; Shenzhen Fundamental Research Program under Grant number JCYJ20210324131809027 and Youth Fund of The Third People’s Hospital of Shenzhen under Grant number G2021008.