Background: The aberrantly expressed circular RNAs (circRNAs) are implicated in the progression of hepatocellular carcinoma (HCC). CircRNA hsa_circ_0006916 (circ_0006916) is dysregulated in HCC, but the function and mechanism of this circRNA in HCC development remain uncertain.
Methods: Thirty paired HCC and normal tissues were collected. circ_0006916, microRNA (miR)-599 and serine/arginine rich splicing factor 2 (SRSF2 ) abundances were examined via quantitative reverse transcription polymerase chain reaction or Western blot. Cell viability, colony ability, migration, invasion, cell cycle and apoptosis were tested via cell counting kit-8, colony formation, wound healing analysis, transwell analysis, and flow cytometry. The interaction between miR-599 and circ_0006916 or SRSF2  was analyzed via dual-luciferase reporter and RNA immunoprecipitation analyses. The function of circ_0006916 on cell growth in vivo was analyzed via xenograft model.
Results: circ_0006916 expression was increased in HCC tissues and cell lines. circ_0006916 knockdown reduced cell viability, colony formation, migration and invasion and caused cell cycle arrest and apoptosis. miR-599 was targeted via circ_0006916, and miR-599 knockdown reversed the influence of circ_0006916 silence on HCC progression. SRSF2  was targeted via miR-599, and miR-599 overexpression suppressed cell viability, colony formation, migration and invasion and promoted cell cycle arrest and apoptosis via decreasing SRSF2 . circ_0006916 could regulate SRSF2  expression via miR-599. circ_0006916 knockdown decreased HCC cell growth in the xenograft model.
Conclusion: circ_0006916 knockdown represses the progression of HCC via regulating miR-599 and SRSF2 .
Keywords: hepatocellular carcinoma, circ_0006916, miR-599, SRSF2