circMRPS35 promotes malignant progression and cisplatin resistance in hepatocellular cancer

Abstract

Hepatocellular carcinoma (HCC), a common malignant tumor, is one of the main causes of cancer-related deaths worldwide. Circular RNAs (circRNAs), a novel class of non-coding RNA, have been reported to be involved in the etiology of various malignancy. However, the functions of circRNAs in HCC remain unclear. In this study, through mining the RNA sequencing databases from GEO datasets and subsequent experimental verification, we identified that hsa_circ_0000384 (circMRPS35) was highly expressed in HCC. Knockdown of circMRPS35 suppressed the proliferation, migration, invasion, clone formation and cell cycle of HCC cell lines both in vitro and in a xenograft mouse model. Mechanically, circMRPS35 sponged microRNA-148a-3p (miR-148a), which in turn regulated STX3-PTEN axis. Surprisingly, we detected a peptide encoded by circMRPS35 (circMRPS35-168aa), which was significantly induced by chemotherapeutic drugs and promoted cisplatin resistance in HCC cells. These results demonstrated that circMRPS35 might be a novel factor in HCC progress, and has a great potential as a new diagnosis and therapeutic target for treatment of HCC.