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| 论文摘要： | Circular RNAs (circRNAs), a class of widespread endogenous RNAs, play crucial roles in diverse biological processes and are potential biomarkers in diverse human diseases and cancers. Cerebellar-degeneration-related protein 1 antisense RNA (CDRlas), an oncogenic circRNA, is involved in human tumorigenesis and is dysregulated in hepatocellular carcinoma (HCC). However, the molecular mechanisms underlying CDRlas functions in HCC remain unclear. Here we explored the functions of CDR1as and searched for CDRlas-regulated proteins in HCC cells. A quantitative proteomics strategy was employed to globally identify CDRlas-regulated proteins in HCC cells. In total, we identified 330 differentially expressed proteins (DEPs) upon enhanced CDRlas expression in HepG2 cells, indicating that they could be proteins regulated by CDRlas. Bioinformatic analysis revealed that many DEPs were involved in cell proliferation and the cell cycle. Further functional studies of epidermal growth factor receptor (EGFR) found that CDRlas exerts its effects on cell proliferation at least in part through the regulation of EGFR expression. We further confirmed that CDRlas could inhibit the expression of microRNA-7 (miR-7). EGFR is a validated target of miR-7; therefore, CDRlas may exert its function by regulating EGFR expression via targeting miR-7 in HCC cells. Taken together, we revealed novel functions and underlying mechanisms of CDRlas in HCC cells. This study serves as the first proteome-wide analysis of a circRNA-regulated protein in cells and provides a reliable and highly efficient method for globally identifying circRNA-regulated proteins. |
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