Depressing hsa_circ_0058092 functions an integrated anti-proliferation and anti-motility role in gastric cancer partially through targeting miR-1294/SIX1 axis

Abstract

AbstractFibronectin 1-derived circular RNA hsa_circ_0058092 is a novel potential oncogene in gastric cancer (GC). Yet, previous studies have not determined the role of hsa_circ_0058092 GC progression and the underlying mechanism. Herein, we investigated its role and competing endogenous RNA (ceRNA) pathway in the development of GC. The results showed that hsa_circ_0058092 was substantially upregulated in GC patients’ tissues and cells, allied with upregulated SIX1 and downregulated miR-1294 compared with normal gastric tissues and cells. There were linear correlations among hsa_circ_0058092, miR-1294 and SIX1 levels in GC tumors. Moreover, hsa_circ_0058092 acted as a miR-1294 sponge, and miR-1294 targeted SIX1. Functionally, colony formation, EdU positive rate, tumor growth of GC cells, as well as ki-67 expression in xenograft tumors was greatly suppressed by depressing hsa_circ_0058092. Besides, hsa_circ_0058092 knockdown repressed GC cell migration and invasion, accompanied with increased E-cadherin expression and descended N-cadherin expression. Moreover, inhibiting miR-1294 expression could counteract hsa_circ_0058092 knockdown-mediated effects in GC cells. The inhibitory effects of miR-1294 mimics on GC cell malignancy were relieved by increasing SIX1 expression. Further, hsa_circ_0058092 depletion repressed SIX1 protein expression by interacting with miR-1294. Hsa_circ_0058092 was oncogenic in GC cell proliferation and motility via ceRNA pathway of hsa_circ_0058092/miR-1294/SIX1.