Purpose: Circular RNAs (circRNAs) play important roles in hepatocellular carcinoma (HCC) development. The circRNA hsa_circ_0091579  (circ_0091579 ) is dysregulated in HCC, while the mechanism of circ_0091579  in HCC development is largely unknown.
Patients and Methods: Thirty paired cancer and adjacent normal tissues were harvested from HCC patients. SNU-387 and Huh7 cells were cultured in this study. circ_0091579 , microRNA-940  (miR-940 ) and tachykinin-1 receptor  (TACR1 ) abundances were measured via quantitative reverse transcription-polymerase chain reaction or Western blot. Cell viability, migration, invasion, colony ability, cell cycle distribution and apoptosis were assessed via 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, transwell assay, colony formation assay and flow cytometry. The interaction among circ_0091579 , miR-940  and TACR1  was tested via dual-luciferase reporter analysis. The anti-HCC role of circ_0091579  knockdown in vivo was investigated using xenograft model.
Results: circ_0091579  expression was enhanced in HCC tissue samples and cells. circ_0091579  silence inhibited cell viability, migration, invasion and colony formation, induced cell cycle arrest at G0/G1 phase, and promoted apoptosis in HCC cells. miR-940  was targeted via circ_0091579  and miR-940  knockdown reversed the suppressive effect of circ_0091579  silence on HCC development. miR-940  targeted TACR1 to repress HCC development. circ_0091579  could regulate TACR1  expression by mediating miR-940 . Down-regulation of circ_0091579  decreased xenograft tumor growth.
Conclusion: Knockdown of circ_0091579  repressed HCC development by mediating miR-940 /TACR1  axis, indicating a new pathogenesis of HCC.
Keywords: hepatocellular carcinoma, hsa_circ_0091579 , miR-940 , TACR1