MiR-142-3p functions as a tumor suppressor by targeting CD133, ABCG2, and Lgr5 in colon cancer cells
MiR-142-3p functions as a tumor suppressor by targeting CD133, ABCG2, and Lgr5 in colon cancer cells
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MiR-142-3p 通过靶向结肠癌细胞中的 CD133、ABCG2 和 Lgr5 发挥肿瘤抑制因子的作用
DOI：
10.1007/s00109-013-1037-x
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发表时间：
2013-08-01
影响因子：
4.7
通讯作者：
Fu, Guo-Hui
中科院分区：
文献类型：
--
作者：
Shen, Wei-Wei;Zeng, Zhi;Fu, Guo-Hui
研究表明，CD 133、富含亮氨酸重复序列的G蛋白偶联受体5（Lgr 5）和ATP结合盒（ABC）G2蛋白的表达与结肠癌的恶性程度和不良预后相关。然而，这三种蛋白的分子调控机制尚未阐明。在这里，我们报告了microRNA-142- 3 p（miR-142- 3 p）通过结合3 '非翻译区和这三个基因的编码序列来抑制结肠癌细胞中CD 133、Lgr 5和ABCG 2的表达。miR-142- 3 p在结肠癌标本中显著降低，其中其与CD 133、Lgr 5和ABCG 2的表达呈负相关。miR-142- 3 p的减少对应于结肠癌中分化差和肿瘤尺寸较大。此外，与在常规培养基中培养的细胞相比，在形成球体的细胞中miR-142- 3 p水平降低。在结肠癌细胞中转染miR-142- 3 p模拟物可下调细胞周期蛋白D1的表达，诱导G（1）期细胞周期阻滞，并提高细胞对5-氟尿嘧啶的敏感性。此外，OCT 4抑制miR-142- 3 p，OCT 4启动子的低甲基化与miR-142- 3 p的减少相关。最后，miR-142- 3 p在体内抑制结肠癌细胞的生长，这伴随着肿瘤组织中CD 133、Lgr 5和ABCG 2的下调。我们的研究结果阐明了结肠癌细胞中一种新的调控途径，并为结肠癌的治疗提供了一种潜在的治疗方法。
Studies have shown that the expression of CD133, leucine-rich-repeat-containing G-protein-coupled receptor 5 (Lgr5), and ATP binding cassette (ABC)G2 proteins is associated with malignancy and poor prognosis in colon cancer. However, molecular regulation mechanism of the three proteins has not been elucidated. Here, we report that microRNA-142-3p (miR-142-3p) inhibits the expression of CD133, Lgr5, and ABCG2 in colon cancer cells by binding to both the 3'-untranslated region and the coding sequences of the three genes. The miR-142-3p was markedly decreased in colon cancer specimens, in which it was negatively correlated with the expression of CD133, Lgr5, and ABCG2. Reduction of miR-142-3p corresponds to poor differentiation and bigger tumor size in colon cancers. Moreover, miR-142-3p levels were reduced in cells that formed spheres compared to cells that were cultured in regular media. Transfection of miR-142-3p mimics in colon cancer cells downregulated cyclin D1 expression, induced G(1) phase cell cycle arrest, and elevated the sensitivity of the cells to 5-fluorouracil. Furthermore, OCT4 suppressed miR-142-3p, and hypomethylation of the OCT4 promoter was associated with a reduction in miR-142-3p. Finally, the miR-142-3p inhibited the growth of colon cancer cells in vivo, which was accompanied by the downregulation of CD133, Lgr5, and ABCG2 in tumor tissues. Our results elucidate a novel regulation pathway in colon cancer cells and suggest a potential therapeutic approach for colon cancer therapy.