microRNA-365, down-regulated in colon cancer, inhibits cell cycle progression and promotes apoptosis of colon cancer cells by probably targeting Cyclin D1 and Bcl-2
microRNA-365, down-regulated in colon cancer, inhibits cell cycle progression and promotes apoptosis of colon cancer cells by probably targeting Cyclin D1 and Bcl-2
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microRNA-365 在结肠癌中下调，可能通过靶向 Cyclin D1 和 Bcl-2 抑制细胞周期进程并促进结肠癌细胞凋亡
DOI：
10.1093/carcin/bgr245
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发表时间：
2012-01-01
期刊：
影响因子：
4.7
通讯作者：
Han, Weidong
中科院分区：
文献类型：
--
作者：
Nie, Jing;Liu, Lin;Han, Weidong
失调的microRNA参与了癌症发生和癌症进展，但它们在癌症发展中的作用仍不清楚。在这项研究中，发现miR-365在人结肠癌组织中的表达与匹配的非肿瘤性粘膜组织相比下调，并且其下调与结肠癌患者的癌症进展和不良生存相关。功能研究显示，miR-365表达的恢复抑制细胞周期进程，促进5-氟尿嘧啶诱导的凋亡，并抑制结肠癌细胞系的致瘤性。此外，通过生物信息学预测和实验验证，发现miR-365的抗肿瘤作用可能是通过靶向抑制Cyclin D1和Bcl-2的表达，从而抑制细胞周期进程，促进细胞凋亡。这些结果表明，miR-365在结肠癌中的下调可能在结肠癌患者的预后预测和基因治疗中具有潜在的应用价值。
Deregulated microRNAs participate in carcinogenesis and cancer progression, but their roles in cancer development remain unclear. In this study, miR-365 expression was found to be downregulated in human colon cancer tissues as compared with that in matched non-neoplastic mucosa tissues, and its downregulation was correlated with cancer progression and poor survival in colon cancer patients. Functional studies revealed that restoration of miR-365 expression inhibited cell cycle progression, promoted 5-fluorouracil-induced apoptosis and repressed tumorigenicity in colon cancer cell lines. Furthermore, bioinformatic prediction and experimental validation were used to identify miR-365 target genes and indicated that the antitumor effects of miR-365 were probably mediated by its targeting and repression of Cyclin D1 and Bcl-2 expression, thus inhibiting cell cycle progression and promoting apoptosis. These results suggest that downregulation of miR-365 in colon cancer may have potential applications in prognosis prediction and gene therapy in colon cancer patients.