Circular RNA Circ-STIL Contributes to Cell Growth and Metastasis in Hepatocellular Carcinoma via Regulating miR-345-5p/AQP3 Axis.

Background: Circular RNAs (circRNAs) are implicated in the pathogenesis and development of hepatocellular carcinoma (HCC). However, the function and latent mechanism of circ-STIL in HCC have not been elucidated.

Aims: This study was designed to explore the precise role and underlying molecular mechanism of circ-STIL in HCC advancement.

Methods: The expression levels of circ-STIL, SCL/TAL1 interrupting locus (STIL), miR-345-5p and aquaporin-3 (AQP3) were measured by quantitative real-time polymerase chain reaction or western blot. Cell proliferation was assessed by 3-(4,5-dimethylthizol-2-yl)-2,5-diphenyltetrazolium bromide assay and colony formation assay. Cell apoptosis was analyzed by flow cytometry. Transwell assay was conducted to analyze cell migratory and invasive capacities. The interactions among circ-STIL, miR-345-5p and AQP3 were confirmed by dual-luciferase reporter and RNA immunoprecipitation assays. Xenograft tumor model was established to analyze the role of circ-STIL in HCC in vivo.

Results: Circ-STIL was upregulated in HCC tissues and cells. Circ-STIL knockdown inhibited HCC cell progression by reducing cell proliferation, migration and invasion and promoting cell apoptosis. MiR-345-5p was a direct target of circ-STIL, and AQP3 was targeted by miR-345-5p in HCC. Circ-STIL knockdown or miR-345-5p overexpression impeded cell malignant behaviors in HCC cells, and the effects could be reversed by miR-345-5p silence or AQP3 enhancement, respectively. Meanwhile, circ-STIL regulated AQP3 expression by sponging miR-345-5p. Besides, circ-STIL downregulation retarded HCC tumor growth in vivo.

Conclusion: Circ-STIL knockdown suppressed HCC development by regulating miR-345-5p/AQP3 pathway, which might provide a promising target for HCC therapy.