CircRNA-104718 acts as competing endogenous RNA and promotes hepatocellular carcinoma progression through microRNA-218-5p/TXNDC5 signaling pathway

Abstract

Accumulating evidences indicate that circular RNAs (circRNAs) play a vital role in diverse cancer biology. However, the contributions of circRNAs to hepatocellular carcinoma (HCC) and their underlying mechanism remain largely unknown. The present study aims at investigating the role of circRNA-104718 in HCC progression, which has been observed to be significantly up-regulated in HCC tissues. We found that, higher expression of circRNA-104718 also leds to a poor prognosis in HCC patients. Using luciferase binding assays and RNA immunoprecipitation studies, we identified circRNA-104718 is physically associated and co-expressed with microRNA (miR)-218-5p in HCC. Mechanistically, we demonstrated that circRNA-104718 functions as a competing endogenous RNAs (ceRNAs) and competes with thioredoxin domain-containing protein 5 (TXNDC5) mRNA and directly binds to miR-218-5p. Functionally, we found that ectopically expressed circRNA-104718 accelerated cell proliferation, migration, invasion, and inhibited apoptosis. In vivo studies on a nude mice model showed that circRNA-104718 overexpression could increase the tumor size and the rate of metastasis. Silencing of circRNA-104718 could decrease both the tumor size and metastasis significantly. Conversely, we also observed overexpression of miR-218-5p could in turn decrease the proliferation, migration, invasion, and increase apoptosis. Furthermore, circRNA-104718 could relieve the suppression of miR-218-5p target TXNDC5 and thereby cause an inhibition of miR's functions. In summary, our results indicate that circRNA-104718 acts as a ceRNA and promotes HCC progression through the targeting of miR-218-5p/TXNDC5 signaling pathway. Thus, we propose that circRNA-104718 would be a promising target for HCC diagnosis and therapy.

Keywords: CircRNA-104718; TXNDC5; hepatocellular carcinoma; microRNA-218-5p.