MicroRNA-10a is down-regulated by DNA methylation and functions as a tumor suppressor in gastric cancer cells.
BACKGROUND
MicroRNAs act as posttranscriptional regulators of gene expression in many biological processes. Their deregulations occur commonly in gastric cancer (GC). Although DNA methylation constitutes an important mechanism for microRNA deregulation in cancer, this field largely remains unexplored.


RESULTS
Total RNA was extracted from the tissues of 100 patients with GC and four gastric cancer cell lines. The expression levels of miR-10a were determined by real-time PCR with specific TaqMan probes. Moreover, a functional analysis of miR-10a in regulating cell proliferation, migration and invasion was performed. Subsequently, quantitative methylation-specific PCR (qMSP) was used to detect the DNA methylation status in the CpG islands upstream of miR-10a. In this study, we found that the expression of miR-10a in GC cells was lower than that in normal cells, which was due to the hypermethylation of the CpG islands upstream of miR-10a. We also validated the slightly lower expression of miR-10a in GC tissues than their adjacent non-neoplastic tissues in 100 GC patients and confirmed the hypermethylation of CpG islands upstream of miR-10a in some patients. Furthermore, re-introduction of miR-10a into GC cells was able to inhibit cell proliferation, migration and invasion. Bioinformatic and immunoblot analysis indicated that the tumor suppressor roles of miR-10a in GC cells were possibly through targeting HOXA1.


CONCLUSIONS
Our data indicate that miR-10a acts as a tumor suppressor in GC cells and is partially silenced by DNA hypermethylation in GC, suggesting that miR-10a may serve as a potential diagnostic or therapeutic target of GC.
Department of Surgery, The First Hospital of Shanxi Medical University, Taiyuan, PR China.
Hongyan
H
Jia
Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing, PR China.
Zhengyi
Z
Zhang
Department of Gynecologic Oncology, Chongqing Cancer Institute, Chongqing, PR China.
Dongling
D
Zou
Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing, PR China ; Department of Surgery, The First Hospital of Shanxi Medical University, Taiyuan, PR China.
Bin
B
Wang
Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing, PR China.
Yunmeng
Y
Yan
Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing, PR China.
Min
M
Luo
Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing, PR China.
Lei
L
Dong
Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing, PR China ; Department of Surgery, The First Hospital of Shanxi Medical University, Taiyuan, PR China.
Haixin
H
Yin
Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing, PR China.
Bei
B
Gong
Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing, PR China.
Zheng
Z
Li
Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing, PR China.
Fang
F
Wang
Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing, PR China.
Wei
W
Song
Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing, PR China.
Changzheng
C
Liu
Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing, PR China.
Yanni
Y
Ma
Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing, PR China.
Junwu
J
Zhang
Department of Surgery,The Shanxi Academy of Medical Sciences & Shanxi Dayi Hospital, Taiyuan, PR China.
Haoliang
H
Zhao
Cancer center, The General Hospital of the People's Liberation Army, Beijing, PR China.
Jianxiong
J
Li
Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing, PR China.
Jia
J
Yu
D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis*; D012334:RNA, Neoplasm / Q000096:biosynthesis*; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology
D004273:DNA, Neoplasm; C547183:MIRN10 microRNA, human; D035683:MicroRNAs; D012334:RNA, Neoplasm