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MicroRNA-30b 通过靶向 KRAS、PIK3CD 和 BCL2 在人结直肠癌中发挥肿瘤抑制作用。

MicroRNA-30b functions as a tumour suppressor in human colorectal cancer by targeting KRAS, PIK3CD and BCL2.

机构信息

Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China; Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, People's Republic of China.

出版信息

J Pathol. 2014 Mar;232(4):415-27. doi: 10.1002/path.4309.

Abstract

Colorectal cancer (CRC) is the third most common cancer in the USA. MicroRNAs play important roles in the pathogenesis of CRC. In this study, we investigated the role of miR-30b in CRC and found that its expression was significantly lower in CRC tissues than that in normal tissues. We showed that a low expression level of miR-30b was closely related to poor differentiation, advanced TNM stage and poor prognosis of CRC. Further experiments showed that over-expression of miR-30b suppressed CRC cell proliferation in vitro and tumour growth in vivo. Specifically, miR-30b promoted G1 arrest and induced apoptosis. Moreover, KRAS, PIK3CD and BCL2 were identified as direct and functional targets of miR-30b. MiR-30b directly targeted the 3'-untranslated regions of their mRNAs and repressed their expression. This study revealed functional and mechanistic links between miRNA-30b and oncogene KRAS, PIK3CD and BCL2 in the pathogenesis of CRC. MiR-30b not only plays important roles in the regulation of cell proliferation and tumour growth in CRC, but is also a potential prognostic marker or therapeutic target for CRC. Restoration of miR-30b expression may represent a promising therapeutic approach for targeting malignant CRC.

摘要

结直肠癌(CRC)是美国第三大常见癌症。microRNAs 在 CRC 的发病机制中发挥重要作用。在这项研究中,我们研究了 miR-30b 在 CRC 中的作用,发现其在 CRC 组织中的表达明显低于正常组织。我们表明,miR-30b 的低表达水平与 CRC 的不良分化、晚期 TNM 分期和不良预后密切相关。进一步的实验表明,miR-30b 的过表达可抑制 CRC 细胞的体外增殖和体内肿瘤生长。具体而言,miR-30b 促进 G1 期阻滞并诱导细胞凋亡。此外,KRAS、PIK3CD 和 BCL2 被鉴定为 miR-30b 的直接和功能靶标。miR-30b 可直接靶向其 mRNA 的 3'-非翻译区并抑制其表达。这项研究揭示了 miRNA-30b 与致癌基因 KRAS、PIK3CD 和 BCL2 在 CRC 发病机制中的功能和机制联系。miR-30b 不仅在 CRC 中调节细胞增殖和肿瘤生长中发挥重要作用,而且还是 CRC 的潜在预后标志物或治疗靶点。恢复 miR-30b 的表达可能代表了针对恶性 CRC 的有前途的治疗方法。

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