He Jin Hua, Han Ze Ping, Luo Jin Gen, Jiang Jian Wei, Zhou Jia Bin, Chen Wei Ming, Lv Yu Bing, He Meng Ling, Zheng Lei, Li Yu Guang, Zuo Ji Dong
Department of Laboratory Medicine, Central Hospital of Panyu District, Guangzhou, China.
Digesting Center, Central Hospital of Panyu District, Guangzhou, China.
Front Genet. 2020 Feb 25;11:9. doi: 10.3389/fgene.2020.00009. eCollection 2020.
Circular RNA (circRNA), a type of RNA that is widely expressed in mammalian cells, is considered to be essential in tumorigenesis. CircRNA can regulate target gene expression by interacting with the corresponding microRNA (miRNA). Our preliminary results showed that the expression levels of 1,817 circRNAs were significantly different in colon cancer tissue compared with paracancerous tissue, of which 1,236 were upregulated and 581 were downregulated. By using RT-PCR, we confirmed that the expression of hsa_circ_0007843, hsa_circ_0010575, hsa_circ_0007331, and hsa_circ_0001615 was significantly higher in colon cancer tissue than in normal colonic tissue; however, the expression levels of hsa_circ_0014879 and hsa_circRNA_401801 were not significantly different between normal and neoplastic colonic tissue. Among the circRNAs that were confirmed to be upregulated in colon cancer tissue, hsa_circ_0007843 was also found to be highly expressed in colon cancer SW480 cells. Overexpression of hsa_circ_0007843 promoted the invasion and migration of SW480 cells, whereas its downregulation suppressed their invasion and migration. Overexpression of hsa_circ_0007843 promoted tumor growth, whereas its downregulation inhibited tumor growth. We found that hsa_circ_0007843 interacted with miR-518c-5p and suppressed its expression, and miR-518c-5p interacted with matrix metallopeptidase 2 (MMP2) and promoted its expression and translation. Taken together, this study demonstrated that hsa_circ_0007843 acted as an miRNA sponge to regulate MMP2 expression by removing the inhibitory effect of miR-518c-5p on MMP2 gene translation, which further affected the invasive capability of SW480 cells.
环状RNA(circRNA)是一种在哺乳动物细胞中广泛表达的RNA,被认为在肿瘤发生过程中至关重要。CircRNA可通过与相应的微小RNA(miRNA)相互作用来调节靶基因的表达。我们的初步结果显示,与癌旁组织相比,结肠癌组织中1817种circRNA的表达水平存在显著差异,其中1236种上调,581种下调。通过逆转录聚合酶链反应(RT-PCR),我们证实hsa_circ_0007843、hsa_circ_0010575、hsa_circ_0007331和hsa_circ_0001615在结肠癌组织中的表达明显高于正常结肠组织;然而,hsa_circ_0014879和hsa_circRNA_401801在正常和肿瘤性结肠组织中的表达水平无显著差异。在结肠癌组织中被证实上调的circRNA中,hsa_circ_0007843在结肠癌SW480细胞中也高表达。hsa_circ_0007843的过表达促进了SW480细胞的侵袭和迁移,而其下调则抑制了它们的侵袭和迁移。hsa_circ_0007843的过表达促进了肿瘤生长,而其下调则抑制了肿瘤生长。我们发现hsa_circ_0007843与miR-518c-5p相互作用并抑制其表达,而miR-518c-5p与基质金属蛋白酶2(MMP2)相互作用并促进其表达和翻译。综上所述,本研究表明hsa_circ_0007843作为一种miRNA海绵,通过消除miR-518c-5p对MMP2基因翻译的抑制作用来调节MMP2的表达,这进一步影响了SW480细胞的侵袭能力。