Hao Qin, Zhang Zhongtao
Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
National Clinical Research Center of Digestive Diseases, 100050 Beijing, China.
Gastroenterol Res Pract. 2020 Dec 9;2020:8834359. doi: 10.1155/2020/8834359. eCollection 2020.
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.
环状RNA（circRNAs）属于非编码RNA，在包括癌症在内的多种细胞类型中广泛表达。然而，circRNAs在结直肠癌（CRC）中的功能和机制尚未得到充分研究。在此，我们首先从基因表达综合数据库（GEO）下载并分析了结直肠癌的circRNA表达谱。我们在10对结直肠癌组织和相邻正常组织中鉴定出181种差异表达的circRNAs。有趣的是，我们观察到hsa_circRNA_000166在这些circRNAs中表达上调最为明显。然后，我们证实在结直肠癌组织和细胞系中hsa_circRNA_000166表达上调，并观察到hsa_circRNA_000166的高表达与结直肠癌患者较差的5年生存率相关。接下来，我们通过敲低其表达来研究hsa_circRNA_000166在结直肠癌进展过程中的功能。细胞生长和凋亡检测显示，hsa_circRNA_000166调节结直肠癌细胞系中的细胞生长和凋亡。此外，我们通过生物信息学分析和荧光素酶报告基因检测确定hsa_circRNA_000166靶向miR-326/LASP1通路。最后，抑制miR-326或过表达LASP1能够充分挽救结直肠癌细胞系中异常细胞生长和凋亡。综上所述，我们的结果表明，hsa_circRNA_000166的下调通过海绵吸附miR-326/LASP1通路抑制了结直肠癌发生发展过程中的细胞生长并促进凋亡。
