Hsa_Circ_0000826 inhibits the proliferation of colorectal cancer by targeting AUF1

Many circular RNAs (circRNAs) are reported to be abnormally expressed during the progression of various tumors, and these circRNAs can be used as anti-tumor targets. Therefore, it is important to identify circRNAs that can be used effectively for the clinical diagnosis and treatment of colorectal cancer (CRC). Here, we report that hsa_Circ_0000826 (Circ_0000826), a circRNA with significantly reduced expression level in CRC tissues, is associated with a poor prognosis in patients. The silencing of Circ_0000826 pro-motes the proliferation of CRC cells. Conversely, the overexpression of Circ_0000826 restricted CRC cell proliferation both in vitro and in vivo. Furthermore, Circ_0000826 could target AU-rich element RNA-binding protein 1 (AUF1). AUF1, known as heterogeneous nuclear ribonucleoprotein D (hnRNP D), could bind to the c-MYC 30-UTR and promote c-MYC expression. When Circ_0000826 binds to AUF1, it competitively in-hibits the binding of AUF1 to the c-MYC 30-UTR, which inhibits the c-MYC expression and cell proliferation. These results provide novel insights into the functional mechanism of Circ_0000826 action in CRC pro-gression and indicate its potential use as a therapeutic target in CRC.Copyright (c) 2022, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Limited and Science Press. All rights reserved.

Automated summary

We report a circRNA named hsa_Circ_0000826 (Circ_0000826) that is significantly downregulated in colorectal cancer (CRC) tissues and is associated with a poor prognosis in patients. Silencing Circ_0000826 promotes CRC cell proliferation, while overexpression of Circ_0000826 inhibits CRC cell proliferation. Furthermore, Circ_0000826 can bind to AUF1 and competitively inhibit its binding to c-MYC 30-UTR, leading to decreased c-MYC expression and cell proliferation.