CircRNA_0000392 Promotes Colorectal Cancer Progression by Sponging miR-193a-5p [post]

Hanchen Xu, Yujing Liu, Peiqiu Cheng, Chunyan Wang, Yang Liu, Wenjun Zhou, Yangxian Xu, Guang Ji
2020 unpublished
Background: Circular RNAs (circRNAs), an important member of the non-coding RNA family, have been revealed the role in the pathogenic progression of diseases in recent years, particularly in the malignant progression of cancer. With the application of high-throughput sequencing technology, a large number of circRNAs have been found in tumor tissues, and some circRNAs have demonstrated the role as oncogenic genes. In this study, we analyzed the circRNA expression profile in colorectal cancer
more » ... ) tissues and normal adjacent tissues by high-throughput sequencing, focusing on the circRNA_0000392, a circRNA with significantly increased expression in colorectal cancer tissues, and further investigating its function in the progression of colorectal cancer.Methods: The expression profile of circRNAs in 6 pairs of CRC tissues and normal adjacent tissues was analyzed by RNA-sequencing. We verified the differential circRNAs with expanded samples by qRT-PCR, focused on circRNA_0000392, and evaluated its associations with clinicopathological features. Then we knocked down circRNA_0000392 in CRC cells and evaluated the effect in vitro and in vivo by functional experiments. The dual luciferase assay and RNA pull-down were performed to further explore the downstream potential molecular mechanisms.Results: CircRNA_0000392 was significantly up-regulated in CRC compared with normal adjacent tissues and cell line. The expression level of circRNA_0000392 was positively correlated with the malignant progression of CRC. Functional studies revealed that reducing the expression of circRNA_0000392 could inhibit the proliferation and invasion of CRC both in vitro and in vivo. Mechanistically, circRNA­_0000392 could act as a sponge of miR-193a-5p and regulate the expression of PIK3R3, then affect the activation of the AKT-mTOR pathway in CRC cells.Conclusions: The circRNA_0000392 has the function as an oncogene through miR-193a-5p/PIK3R3-Akt axis in CRC cells, implying that circRNA_0000392 is a potential therapeutic target for the treatment of colorectal cancer and a predictive marker for CRC patients.
doi:10.21203/rs.3.rs-59369/v1 fatcat:cecwooc2lncf7ldpza3rtdga5a