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首页> 外文期刊>Journal of Pathology: Journal of the Pathological Society of Great Britain and Ireland >MicroRNA-30b functions as a tumour suppressor in human colorectal cancer by targeting KRAS, PIK3CD and BCL2
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MicroRNA-30b functions as a tumour suppressor in human colorectal cancer by targeting KRAS, PIK3CD and BCL2

机译:MicroRNA-30b通过靶向KRAS,PIK3CD和BCL2而在人类大肠癌中发挥抑癌作用

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摘要

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.
机译:大肠癌(CRC)是美国第三大最常见的癌症。 MicroRNA在CRC的发病机理中起重要作用。在这项研究中,我们调查了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。我们发现,miR-30b的低表达水平与分化不良,TNM分期晚期和CRC预后不良密切相关。进一步的实验表明,miR-30b的过表达抑制了CRC细胞的体外增殖和体内肿瘤的生长。具体而言,miR-30b促进G1阻滞并诱导凋亡。此外,KRAS,PIK3CD和BCL2被确定为miR-30b的直接和功能靶标。 MiR-30b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与癌基因KRAS,PIK3CD和BCL2在CRC发病机理中的功能和机理联系。 MiR-30b不仅在CRC中调节细胞增殖和肿瘤生长中起重要作用,而且还是CRC的潜在预后标志物或治疗靶标。 miR-30b表达的恢复可能代表靶向恶性CRC的有前途的治疗方法。

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