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