A Novel Circular RNA, circ_0005394, Predicts Unfavorable Prognosis and Contributes to Hepatocellular Carcinoma Progression by Regulating miR-507/E2F3 and miR-515-5p/CXCL6 Signaling Pathways

摘要

Objective: Circular RNAs (circRNAs) play a key role in cancer development and progression. Previously, circ_0005394 was found to be highly expressed in hepatocellular carcinoma (HCC) screened by circRNA microarray. However, the research with regard to the functions and mechanisms of circ_0005394 in HCC remains unknown. Materials and Methods: The expression of circ_0005394 in HCC was measured by qRT-PCR. The clinical relevance was evaluated by Fisher’s exact test, Kaplan–Meier curves, and Cox regression model. Gain/loss-of function assays were performed to elucidate the functions of circ_0005394 in Huh-7 and HepG2 cells. Dual-luciferase reporter assay was applied to reveal the mechanism of circ_0005394. Results: circ_0005394 expression was higher in HCC tissues and cells than noncancerous samples and normal cell line, respectively. High expression of circ_0005394 was associated with larger tumor size, more advanced TNM stages, and poorer overall survival for the patients with HCC. Gain/loss-of function assays demonstrated its oncogenic role in cell growth, apoptosis, migration, and invasion. Mechanistically, miR-507 and miR-515-5p could be sponged by circ_0005394. Furthermore, E2F Transcription Factor 3 (E2F3) and C-X-C motif chemokine ligand 6 (CXCL6) were confirmed as the target of miR-507 and miR-515-5p, respectively. Rescue assay indicated that circ_0005394 facilitated HCC growth and invasion by regulating miR-507/E2F3 and miR-515-5p/CXCL6 signaling pathways. Conclusion: This study uncovered an important role of circ_0005394 in regulating HCC progression, providing a novel perspective for clarifying its pathogenesis.