Background: Studies have demonstrated that circular RNAs (circRNAs) play important roles in various types of cancer; however, the mechanisms of circRNAs located in the nucleus have rarely been explored. Here, we reported a novel circular RNA circPLCE1 facilitates the malignant progression of colorectal cancer (CRC) via repression of SRSF2-dependent PLCE1 pre-RNA splicing.
Methods: qRT-PCR was used to determine the expression of circPLCE1 in CRC tissues and cells. CCK-8, transwell and flow cytometric assays were used to assess the role of circPLCE1 in CRC cell proliferation, migration and apoptosis, respectively. Animal study was carried to test the role of circPLCE1 in vivo. Further, catRAPID and RPISeq were applied to predict the possible binding protein of circPLCE1. RNA fractionation and RIP assays were used to confirm the RNA-protein interaction.
Results: In this study, we found that circPLCE1 was significantly downregulated in CRC tissues compared with adjacent normal tissues. However, circPLCE1 knockdown suppresses CRC cell proliferation, migration, invasion and increased apoptosis. Nude mice experiments showed that ectopic expression of circPLCE1 dramatically increased tumor growth in vivo. Mechanically, circPLCE1 directly binding to SRSF2 protein, repressing SRSF2-dependent PLCE1 pre-RNA splicing, resulting in the progression of CRC. Individually mutating the binding sites of circPLCE1 derepressed the production of PLCE1 mRNA.
Conclusions: Our studies revealed a novel molecular mechanism in the regulation of PLCE1 and implicated a new function of circular RNA, supporting the pursuit of circPLCE1 as a potential tool for future CRC treatment.