PUMA 是人类上皮性癌症中 miR-221/222 的一个新靶点。

PUMA is a novel target of miR-221/222 in human epithelial cancers.

机构信息

Department of Neurosurgery, Tianjin Medical University General Hospital, Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin, PR China.

出版信息

Int J Oncol. 2010 Dec;37(6):1621-6. doi: 10.3892/ijo_00000816.

DOI:10.3892/ijo_00000816

PMID:21042732

Abstract

miR-221 and miR-222 (miR-221/222) are frequently up-regulated in human epithelial cancers. However, the mechanism of miR-221/222 action involved in carcinogenesis has not been extensively studied. Here, we found that reduction of miR-221/222 inhibited cell proliferation and induced mitochondrial-mediated apoptosis in human epithelial cancer cells (A549 lung cancer and MCF-7 breast cancer cells). Bioinformatics and luciferase reporter assays showed that miR-221/222 co-modulated the p53 upregulated modulator of apoptosis (PUMA) expression by directly targeting the binding site within the 3'UTR. Together, these findings suggest that PUMA is a direct target of miR-221/222 that functions as an endogenous apoptosis regulator in these epithelial cancers.

摘要

miR-221 和 miR-222（miR-221/222）在人类上皮性癌症中经常上调。然而，miR-221/222 参与致癌作用的机制尚未得到广泛研究。在这里，我们发现降低 miR-221/222 抑制了人类上皮性癌细胞（肺癌 A549 细胞和乳腺癌 MCF-7 细胞）的增殖并诱导了线粒体介导的细胞凋亡。生物信息学和荧光素酶报告基因检测显示，miR-221/222 通过直接靶向 3'UTR 中的结合位点共同调节 p53 上调凋亡调节剂（PUMA）的表达。综上所述，这些发现表明 PUMA 是 miR-221/222 的直接靶标，在这些上皮性癌症中作为内源性凋亡调节剂发挥作用。