MicroRNA-10a is down-regulated by DNA methylation and functions as a tumor suppressor in gastric cancer cells.

Autor:	Jia H; Department of Surgery, The First Hospital of Shanxi Medical University, Taiyuan, PR China., Zhang Z; Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing, PR China., Zou D; Department of Gynecologic Oncology, Chongqing Cancer Institute, Chongqing, PR China., Wang B; 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., Yan Y; Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing, PR China., Luo M; Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing, PR China., Dong L; Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing, PR China., Yin H; 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., Gong B; Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing, PR China., Li Z; Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing, PR China., Wang F; Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing, PR China., Song W; Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing, PR China., Liu C; Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing, PR China., Ma Y; Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing, PR China., Zhang J; Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing, PR China., Zhao H; Department of Surgery,The Shanxi Academy of Medical Sciences & Shanxi Dayi Hospital, Taiyuan, PR China., Li J; Cancer center, The General Hospital of the People's Liberation Army, Beijing, PR China., Yu J; Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing, PR China.
Jazyk:	angličtina
Zdroj:	PloS one [PLoS One] 2014 Jan 31; Vol. 9 (1), pp. e88057. Date of Electronic Publication: 2014 Jan 31 (Print Publication: 2014).
DOI:	10.1371/journal.pone.0088057
Abstrakt:	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. Methodology/principal Findings: 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/significance: 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.
Databáze:	MEDLINE
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