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

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.

Graphical abstract

KEYWORDS:

• circ_0008043
• hepatocellular carcinoma
• miR-326
• RAB21
• proliferation
• invasion

Highlights

1. Circ_0008043 is highly expressed in liver cancer.

2. Interfering with circ_0008043 inhibits HCC cell migration and invasion.

3. Circ_0008043/miR-326/RAB21 axis promotes HCC progression.

Data Availability Statement

The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.

Ethical approval

This study protocol was approved by the Ethics Committee of Shenzhen Third People’s Hospital 202002703 on 1st of February in 2021.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

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.