Hsa_Circ_0000826 inhibits the proliferation of colorectal cancer by targeting AUF1

Colorectal cancer (CRC) is a common malignant tumor. More than 1.2 million patients are diagnosed with CRC every year, and the number of CRC-related deaths exceeds 600,000; thus, CRC is becoming increasingly harmful to humans (Siegel et al., 2021). Although some progress has been achieved in the early diagnosis and treatment of CRC in recent years, the overall effectiveness of the treatment process is not obvious. The specific molecular mechanisms underlying the occurrence and metastasis of CRC need to be fully understood. This can be achieved via the elucidation of the pathogenesis of CRC and the identification of clinically significant molecular markers and drug targets for the disease.

Recently, several studies have reported on the presence of circular RNAs (circRNAs) in mammals (Huang et al., 2020; Zhou et al., 2020). CircRNAs are formed by reverse head-to-tail shearing and highly conserved (Goodall and Wickramasinghe, 2020). CircRNAs act as miRNA sponges in the cells, blocking or reducing the inhibitory effect of miRNAs on genes, thereby promoting the expression of target genes (Qu et al.,2015; Piwecka et al., 2017). CircRNAs can also directly bind to protein molecules and affect the function of related proteins, thereby regulating tumorigenesis and development (Ashwal-Fluss et al., 2014; Du et al., 2016). However, the role of circRNAs in CRC development has been studied rarely. Several circRNAs related to CRC have been identified, and the specific functions and molecular regulatory mechanisms of most circRNAs are not clear.

In our previous study, we sequenced and analyzed cancer tissues and surrounding normal intestinal mucosal tissues of CRC patients, and selected 23 circRNAs that exhibited significant differential expression, among which 3 were upregulated and 20 were downregulated (Zhang et al., 2019). Among these circRNAs, the expression of hsa_Circ_0000826 (Circ_0000826) was significantly different between healthy colorectal tissues and colorectal cancer tissues (Zhang et al., 2019). RT-qPCR analysis revealed a significantly lower expression level of hsa_circ_0000826 in 27 of the 30 CRC specimens, as compared to adjacent healthy tissues. In comparison with healthy NCM460 colorectal epithelial cells, the expression levels of Circ_0000826 were downregulated in the SW620, HCT116, HCT8, LoVo, Caco2, SW480, and RKO CRC cell lines (Zhang et al., 2019). We selected Circ_0000826 as the focus of our research. Here, we will further explore the functional role of Circ_0000826 in CRC and its specific regulatory molecular mechanisms in cell and animal models. Our findings may help us identify effective targets for colorectal cancer drugs.

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