MiR-138 inhibits tumor growth through repression of EZH2 in non-small cell lung cancer.
OBJECTIVE
MicroRNAs (miRNAs) play important roles in tumorigenesis. We investigated the roles and mechanisms of miR-138 in human non-small cell lung cancer (NSCLC).


METHODS
The expression of miR-138 was first examined in NSCLC cell lines and tumour tissues by real-time PCR The in vitro and in vivo functional effect of miR-138 was examined further. A luciferase reporter assay was conducted to confirm target association between miR-138 and the enhancer of zeste homolog 2 (EZH2).


RESULTS
miR-138 was frequently downregulated in NSCLC cells and tissues. Overexpression of miR-138 inhibited proliferation of NSCLC cells in vitro and tumor growth in vivo. The EZH2 oncogene, which is often overexpressed in various human cancers and acts as an important regulator of cell growth and tumor invasion, was identified as a novel target of miR-138. miR-138 can bind to the 3' untranslated region (3' UTR) of EZH2 and suppress the expression of EZH2 at both mRNA and protein levels. Furthermore, knockdown of EZH2 phenocopied the tumor suppressive effects of miR-138 in cell models, whereas ectopic expression of EZH2 rescued the suppressive effects of miR-138.


CONCLUSIONS
These findings define a tumor suppressor function for miR-138 in NSCLC and further suggest that miR-138 may represent a potential therapeutic target for NSCLC patients.
Department of Anesthesiology, Shanghai Pulmonary Hospital, Tongji University, Shanghai.
Huijun
H
Zhang
Hui
H
Zhang
Mingchuan
M
Zhao
Zhongwei
Z
Lv
Xiaoping
X
Zhang
Xiong
X
Qin
Heyong
H
Wang
Shaohua
S
Wang
Jinmei
J
Su
Xin
X
Lv
Hongcheng
H
Liu
Weijia
W
Du
Wenyong
W
Zhou
Xiaofeng
X
Chen
Ke
K
Fei
D020413:3' Untranslated Regions; D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D015536:Down-Regulation; D000071221:Enhancer of Zeste Homolog 2 Protein; D059585:G1 Phase Cell Cycle Checkpoints; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D063151:Polycomb Repressive Complex 2 / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D014183:Transplantation, Heterologous
D020413:3' Untranslated Regions; C546110:MIRN138 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2