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miR-449b 通过下调 CCND1 和 E2F3 的表达抑制 SW1116 结肠癌细胞干细胞的增殖。

miR-449b inhibits the proliferation of SW1116 colon cancer stem cells through downregulation of CCND1 and E2F3 expression.

机构信息

Department of General Surgery, Huashan Hospital Affiliated to Fudan University, Shanghai 200040, P.R. China.

出版信息

Oncol Rep. 2013 Jul;30(1):399-406. doi: 10.3892/or.2013.2465. Epub 2013 May 14.

DOI:10.3892/or.2013.2465
PMID:23674142
Abstract

Colorectal cancer is one of the leading causes of cancer-related mortality worldwide. Cancer stem cells are cell populations with stem cell nature presenting in tumor tissues and are the root of tumor formation and metastasis. CCND1 and E2F3 play important roles in cell cycle regulation. The 3'UTRs of CCND1 and E2F3 contain miR-449 binding sites. By transfecting pre-miR-449b and inhibiting miR-449b, we found that cell cycle, cell proliferation ability and cell cycle regulatory protein expression levels of colon cancer stem cells were altered. The correlation between CCND1, E2F3 and miR-449b showed that miR-449b could downregulate CCND1 and E2F3 expression. This, in turn, reduced the proliferative ability of colon cancer stem cells. These data suggest that miR-449b plays a tumor-suppressive role in colon cancer stem cells.

摘要

结直肠癌是全球癌症相关死亡的主要原因之一。癌症干细胞是存在于肿瘤组织中的具有干细胞特性的细胞群体,是肿瘤形成和转移的根源。CCND1 和 E2F3 在细胞周期调控中发挥重要作用。CCND1 和 E2F3 的 3'UTR 含有 miR-449 结合位点。通过转染 pre-miR-449b 并抑制 miR-449b,我们发现结肠癌干细胞的细胞周期、增殖能力和细胞周期调节蛋白表达水平发生了改变。CCND1、E2F3 和 miR-449b 之间的相关性表明,miR-449b 可以下调 CCND1 和 E2F3 的表达。这反过来又降低了结肠癌干细胞的增殖能力。这些数据表明,miR-449b 在结肠癌干细胞中发挥肿瘤抑制作用。

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