Circular RNA 0060745, a Novel circRNA, Promotes Colorectal Cancer Cell Proliferation and Metastasis Through miR-4736 Sponging.

PURPOSE

Recent studies have shown that noncoding RNAs (ncRNAs) play essential roles in the development of a number of cancers. Circular RNAs (circRNAs) have been shown to contribute to the progression of colorectal cancer (CRC).

METHODS

In this study, the expression levels of circular RNA 0060745 (circ_0060745), and microRNA 4736 (miR-4736) were measured using qRT-PCR. Kaplan-Meier survival analysis and receiver operating characteristic (ROC) analysis were used to evaluate the diagnostic value of circ_0060745. Transwell assay and cell counting kit-8 (CCK8) assay were used to determine the metastatic and proliferative capacity of CRC cells. The expression of chromosome segregation one like (CSE1L) was measured using Western blotting and immunohistochemistry (IHC). In addition, RNA pull-down assay and luciferase assay were performed to verify the targeted binding between miR-473,6 and circ_0060745, and between as miR-4736 and CSE1L.

RESULTS

We showed that circ_0060745 was upregulated in CRC, and was associated with unfavorable clinicopathological characteristics. We also showed that circ_0060745 acted as an oncogene and promoted CRC cell proliferation and metastasis. Circ_0060745 was primarily located in the cytoplasm. Furthermore, miR-4736 was downregulated in CRC, was a downstream target of circ_0060745, and mediated proliferation and metastasis. We showed that circ_0060745 sequestered miR-4736, which resulted in CRC cell proliferation and metastasis. Finally, we showed that CSE1L, a downstream target of miR-4736, was upregulated in CRC and mediated suppression of proliferation and metastasis in CRC.

CONCLUSION

The results of this study showed that circ_0060745 promoted CRC cell proliferation and metastasis via modulation of miR-4736/CSE1L signaling. The Circ_0060745/miR-4736/CSE1L axis might be a novel target for the treatment of CRC.