MiR-26a inhibits cell growth and tumorigenesis of nasopharyngeal carcinoma through repression of EZH2

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

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Author(s)

  • Juan Lu
  • Lu Wang
  • Ying Chen
  • Xiong Liu
  • Qi Dong
  • Yang-Chao Chen
  • Ying Peng
  • Kai-Tai Yao
  • Hsiang-Fu Kung
  • Xiang-Ping Li

Detail(s)

Original languageEnglish
Pages (from-to)225-233
Journal / PublicationCancer Research
Volume71
Issue number1
Publication statusPublished - 1 Jan 2011
Externally publishedYes

Abstract

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 G1-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 p14ARF and p21CIP1 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. ©2011 AACR.

Citation Format(s)

MiR-26a inhibits cell growth and tumorigenesis of nasopharyngeal carcinoma through repression of EZH2. / Lu, Juan; He, Ming-Liang; Wang, Lu; Chen, Ying; Liu, Xiong; Dong, Qi; Chen, Yang-Chao; Peng, Ying; Yao, Kai-Tai; Kung, Hsiang-Fu; Li, Xiang-Ping.

In: Cancer Research, Vol. 71, No. 1, 01.01.2011, p. 225-233.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review