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MicroRNA-199a-5p suppresses the cell growth of colorectal cancer by targeting oncogene Caprin1
3 Biotech ( IF 2.8 ) Pub Date : 2020-09-26 , DOI: 10.1007/s13205-020-02433-9
Xiangyang Yu 1 , Yanfang He 2 , Yan Wang 2 , Yajuan Tang 2 , Yanjuan Guo 2 , Jinling Yuan 2 , Jinghe Bai 2 , Tao Yao 2 , Xiongzhi Wu 1
Affiliation  

MicroRNAs-199a-5p (miR-199a-5p) plays critical regulatory roles in various types of human cancers. However, the biological function and regulatory mechanisms of miR-199a-5p in colorectal cancer (CRC) remain unclear. The aim of this study was to investigate the role of miR-199a-5p in CRC and possible mechanisms of its action. The expression of miR-199a-5p in CRC tumor tissues was validated using quantitative real-time PCR (qRT-PCR). The effects of miR-199a-5p on cell proliferation and apoptosis were evaluated in vitro. Then, the association of miR-199a-5p and its downstream target was investigated in both cell line and clinical specimens. Furthermore, gain- and loss-of-function studies of cytoplasmic activation/proliferation-associated protein-1 (Caprin1) were performed to assess whether the suppressive effect of on CRC cells were via targeting Caprin1. Using a microarray platform, we focused on miR-199a-5p for further research, which was one of the most markedly downregulated miRNAs in CRC tumor tissues. Functionally, the overexpression of miR-199a-5p inhibited proliferation and induced apoptosis in both HTC116 and SW480 cells. Furthermore, cytoplasmic activation/proliferation-associated protein-1 (Caprin1), a well-known oncogene, was directly targeted by miR-199a-5p. It was also observed that Caprin1 was upregulated, and inversely correlated with miR-199a-5p levels in CRC tissues. Further investigations revealed that knockdown of Caprin1 by siRNA has similar role with miR-199a-5p overexpression in CRC cells, suggesting the oncogenic role of Caprin1 in CRC. In the contrast, we found that overexpression of Caprin1 reversed the suppressive effects of miR-199a-5p on CRC cells. Collectively, our study suggests that miR-199a-5p/Caprin1 axis may serve as potential therapeutic targets for the treatment of CRC.



中文翻译:

MicroRNA-199a-5p 通过靶向癌基因 Caprin1 抑制结直肠癌的细胞生长

MicroRNAs-199a-5p (miR-199a-5p) 在各种类型的人类癌症中发挥关键的调节作用。然而,miR-199a-5p 在结直肠癌 (CRC) 中的生物学功能和调控机制仍不清楚。本研究的目的是研究 miR-199a-5p 在 CRC 中的作用及其可能的作用机制。使用定量实时 PCR (qRT-PCR) 验证 miR-199a-5p 在 CRC 肿瘤组织中的表达。在体外评估了 miR-199a-5p 对细胞增殖和凋亡的影响。然后,在细胞系和临床标本中研究了 miR-199a-5p 与其下游靶标的关联。此外,进行了细胞质激活/增殖相关蛋白-1 (Caprin1) 的功能获得和丧失研究,以评估对 CRC 细胞的抑制作用是否通过靶向 Caprin1。使用微阵列平台,我们专注于 miR-199a-5p 进行进一步研究,它是 CRC 肿瘤组织中最显着下调的 miRNA 之一。在功能上,miR-199a-5p 的过表达抑制了 HTC116 和 SW480 细胞的增殖并诱导了细胞凋亡。此外,细胞质激活/增殖相关蛋白-1 (Caprin1),一种众所周知的癌基因,直接被 miR-199a-5p 靶向。还观察到 Caprin1 被上调,并且与 CRC 组织中的 miR-199a-5p 水平呈负相关。进一步的研究表明,siRNA 对 Caprin1 的敲低与 CRC 细胞中的 miR-199a-5p 过表达具有相似的作用,这表明 Caprin1 在 CRC 中的致癌作用。相比之下,我们发现 Caprin1 的过表达逆转了 miR-199a-5p 对 CRC 细胞的抑制作用。总的来说,我们的研究表明 miR-199a-5p/Caprin1 轴可作为治疗 CRC 的潜在治疗靶点。

更新日期:2020-09-26
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