MiR-26a Inhibits Cell Growth and Tumorigenesis of Nasopharyngeal Carcinoma through Repression of EZH2
Publication in refereed journal


摘要Several microRNAs (miRNA) have been implicated in nasopharyngeal carcinoma (NPC), a highly invasive and metastatic cancer that is widely prevalent in southern China. In this study, we report that microRNA miR-26a is commonly downregulated in NPC specimens and NPC cell lines with important functional consequences. Ectopic expression of miR-26a dramatically suppressed cell proliferation and colony formation by inducing G(1)-phase cell-cycle arrest. We found that miR-26a strongly reduced the expression of EZH2 oncogene in NPC cells. Similar to the restoring miR-26 expression, EZH2 downregulation inhibited cell growth and cell-cycle progression, whereas EZH2 overexpression rescued the suppressive effect of miR-26a. Mechanistic investigations revealed that miR-26a suppressed the expression of c-myc, the cyclin D3 and E2, and the cyclin-dependent kinase CDK4 and CDK6 while enhancing the expression of CDK inhibitors p14(ARF) and p21(CIP1) in an EZH2-dependent manner. Interestingly, cyclin D2 was regulated by miR-26a but not by EZH2, revealing cyclin D2 as another direct yet mechanistically distinct target of miR-26a. In clinical specimens, EZH2 was widely overexpressed and its mRNA levels were inversely correlated with miR-26a expression. Taken together, our results indicate that miR-26a functions as a growth-suppressive miRNA in NPC, and that its suppressive effects are mediated chiefly by repressing EZH2 expression. Cancer Res; 71(1); 225-33. (C) 2011 AACR.
著者Lu JA, He ML, Wang L, Chen Y, Liu XO, Dong Q, Chen YC, Peng Y, Yao KT, Kung HF, Li XP
期刊名稱Cancer Research
出版社American Association for Cancer Research
頁次225 - 233
Web of Science 學科類別Oncology; ONCOLOGY

上次更新時間 2020-29-11 於 23:52