Circular RNA Circ-0003006 Promotes Hepatocellular Carcinoma Proliferation and Metastasis Through Sponging miR-542-3p and Regulating HIF-1A

Abstract

Introduction

Hepatocellular carcinoma (HCC) is one most common cancer types among gastrointestinal cancer over the world, while its underlying mechanisms remain unclear. CircRNA has been revealed to participate in multiple biological functions and contribute to various diseases’ progression.

Methods

Bioinformatic analysis of the differently expressed circRNAs in the HCC tissues, then verified by real-time quantitative PCR (RT-qPCR) assay. We found that circ-0003006 was upregulated in the HCC tissues, the cell fractionation assay and RNA fluorescence in situ hybridization (FISH) were performed to confirm the cell location of circ-0003006. shRNA silence assay was used to knock down the expression of circ-0003006 in the HCC cells.

Results

Cell account kit 8 (CCK-8) and transwell assay were revealed that circ-0003006 knockdown inhibited the proliferation and metastasis in HCC cells. The target miR‑542‑3p and target gene HIF-1A were predicted by bioinformatics analysis, then verified through biotinylated RNA pull-down and dual-luciferase reporter assays. The mechanism, circ-0003006, probably acted as a sponge of miR‑542‑3p and regulated HIF-1A levels in hepatocellular carcinoma cells. Moreover, HIF-1A overexpression abolished the effect of circ-0003006 inhibition on the progression of hepatocellular carcinoma cells. The subcutaneous tumor formation experiment indicated that circ-0003006 knockdown inhibited the HCC cell growth in vivo.

Conclusion

Circ-0003006 was demonstrated to promote HCC progression in vitro and in vivo by sponging miR‑542‑3p to release the inhibition on HIF-1A.

Keywords:

• circular RNA
• circ-0003006
• miR-542-3p
• HIF-1A
• hepatocellular carcinoma

Acknowledgments

We appreciate all participants who provide technical support for our research.

Highlights

(1) circ-0003006 is highly expressed in HCC.

(2) circ-0003006 was induced by ZEB1 in HCC cells.

(3) circ-0003006 affects the proliferation, migration and invasion of HCC cells.

(3) circ-0003006 functions as a sponge of miR-542-3p to upregulate HIF-1A in HCC cells.

Data Sharing Statement

The data used to support the findings of this study are available from the corresponding author upon request.

Ethics Statement

Our study was approved by the Ethics Review Board of the Jiangxi Cancer Hospital of Nanchang University.

Disclosure

The authors declare that they have no competing interests.