Abstract
Circular RNAs (circRNAs) belong to noncoding RNAs and are widely expressed in a variety of cell species, including cancers. However, the function and mechanism of circRNAs in colorectal cancer (CRC) has not been well investigated. Here, we firstly downloaded and analyzed the circRNA expression profile of CRC from the Gene Expression Omnibus (GEO) database. And we identified 181 differentially expressed circRNAs between 10 pairs of CRC and adjacent normal tissues. Interestingly, we observed that the expression of hsa_circRNA_000166 was the top increased among these circRNAs. Then, we confirmed an upregulation of hsa_circRNA_000166 in CRC tissues and cell lines and observed that higher expression of hsa_circRNA_000166 was associated with poor 5-year survival rate of patients with CRC. Next, we investigated the function of hsa_circRNA_000166 during CRC progression by knocking down its expression. Cell growth and apoptosis assay revealed that hsa_circRNA_000166 regulated the cell growth and apoptosis in CRC cell lines. Furthermore, we identified that hsa_circRNA_000166 targeted the miR-326/LASP1 pathway using bioinformatics analysis and luciferase reporter assay. Finally, suppression of miR-326 or overexpression of LASP1 could sufficiently rescue the aberrant cell growth and apoptosis in CRC cell lines. Taken together, our results indicated that downregulation of hsa_circRNA_000166 inhibited the cell growth and facilitated apoptosis during CRC development by sponging the miR-326/LASP1 pathway.
Highlights
Colorectal cancer (CRC) is one of the malignant cancers with the highest incidence and the fourth leading cause of cancerrelated mortality around the world [1]
Despite the advanced surgery technologies and medicine treatments that have been applied in CRC treatment, the survival rate of patients with CRC still remains unsatisfactory [3,4,5,6,7]
We downloaded the circRNA expression microarray dataset GSE126094 associated with colorectal cancer from the Gene Expression Omnibus (GEO) database and normalized (Figure 1(a))
Summary
Colorectal cancer (CRC) is one of the malignant cancers with the highest incidence and the fourth leading cause of cancerrelated mortality around the world [1]. Circular RNAs (circRNAs), a subgroup of noncoding RNAs, have a crucial role in regulating gene expression and function in distinct biological processes [8,9,10,11,12]. Multiple evidences have demonstrated that the expression of circRNAs is aberrant in various cancers [15,16,17,18,19]. CircRNAs mainly served as upstream regulator to control the expression of microRNA (miRNA) during tumorigenesis [16, 20,21,22]. Previous studies have shown that circRNAs have an essential role in CRC progression by the regulation of multiple miRNAs [18, 23, 24]. The function of dysregulated circRNAs during the development of CRC remains to be further elucidated
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