TITLE

DNA methylation downregulated mir-10b acts as a tumor suppressor in gastric cancer

AUTHOR(S)
Li, Zheng; Lei, Huizi; Luo, Min; Wang, Yi; Dong, Lei; Ma, Yanni; Liu, Changzheng; Song, Wei; Wang, Fang; Zhang, Junwu; Shen, Jianxiong; Yu, Jia
PUB. DATE
January 2015
SOURCE
Gastric Cancer;Jan2015, Vol. 18 Issue 1, p43
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Background: MicroRNAs act as tumor suppressors or oncogenes. The pathological roles of miRNAs in gastric tumorigenesis are largely unknown. Although miR-10b was identified as an miRNA deregulator expressed in gastric cancer (GC), there also exists some debate on whether miR-10b is acting as tumor suppressor or oncogene in GC. Methods: Quantitative RT-PCR was employed to investigate the level of miR-10b in GC tissues and matched adjacent normal tissues ( n = 100). In vitro cell proliferation, apoptosis assays, cell migration, and invasion assays were performed to elucidate the biological effects of miR-10b. Because silencing of miRNA by promoter CpG island methylation may be an important mechanism in tumorigenesis, GC cells were treated with 5-aza-2′-deoxycytidine and trichostatin A, and expression changes of miR-10b were subsequently examined by quantitative RT-PCR. Furthermore, the methylation status of the CpG island upstream of miR-10b was analyzed by methylation-specific PCR in GC tissues ( n = 29). Results: We showed here that miR-10b was significantly downregulated in GC cell lines and tissues as demonstrated by quantitative real-time PCR. Overexpression of miR-10b in MGC-803 and HGC-27 dramatically suppressed cell proliferation, migration, invasion, and induced apoptosis. Moreover, we demonstrated that T-cell lymphoma invasion and metastasis (Tiam1) was a target of miR-10b. Furthermore, 5-aza-2′-deoxycytidine and trichostain A increased miR-10b expression, and the methylation level was high in the CpG islands upstream of miR-10b gene. Conclusions: Taken together, these findings suggest that miR-10b may function as a novel tumor suppressor and is partially silenced by DNA hypermethylation in GC.
ACCESSION #
99841074

 

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