SCARB1-encoded circ _0029343 induces p73 splicing to promote growth and metastasis of hepatocellular carcinoma via miR-486-5p/SRSF3 axis.

Abstract

Circular RNAs (circRNAs) exhibit essential regulation in the malignant development of hepatocellular carcinoma (HCC). This study aims to investigate the physiological mechanisms of circ_0029343 encoded by scavenger receptor class B member 1 (SCARB1) involved in the growth and metastasis of HCC. Differentially expressed mRNAs in HCC were obtained, followed by the prediction of target genes of differentially expressed miRNAs and gene ontology and kyoto encyclopedia of genes and genomes analysis on the differentially expressed mRNAs. Moreover, the regulatory relationship between circRNAs encoded by SCARB1 and differentially expressed miRNAs was predicted. In vitro cell experiments were performed to verify the effects of circ_0029343, miR-486-5p, and SRSF3 on the malignant features of HCC cells using the gain- or loss-of-function experiments. Finally, the effects of circ_0029343 on the growth and metastasis of HCC cells in xenograft mouse models were also explored. It was found that miR-486-5p might interact with seven circRNAs encoded by SCARB1, and its possible downstream target gene was SRSF3. Moreover, SRSF3 was associated with the splicing of various RNA. circ_0029343 could sponge miR-486-5p to up-regulate SRSF3 and activate PDGF-PDGFRB (platelet-derived growth factor and its receptor, receptor beta)signaling pathway by inducing p73 splicing, thus promoting the proliferation, migration, and invasion and inhibiting apoptosis of HCC cells. In vivo, animal experiments further confirmed that overexpression of circ_0029343 could promote the growth and metastasis of HCC cells in nude mice. circ_0029343 encoded by SCARB1 may induce p73 splicing and activate thePDGF-PDGFRB signaling pathway through the miR-486-5p/SRSF3 axis, thus promoting the growth and metastasis of HCC cells.