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MicroRNA-144 inhibits the metastasis of gastric cancer by targeting MET expression.

Abstract：

:Gastric cancer (GC) remains one of the most common types of malignant cancer, and the molecular mechanism underlying its metastasis is still largely unclear. MicroRNAs have emerged as important regulators of metastasis because of their ability to act on multiple signaling pathways. In our study, we found that miR-144 is significantly downregulated in both highly metastatic GC cell lines and tissues. Results from both gain-of-function and loss-of-function experiments demonstrate that increased miR-144 expression significantly reduced GC cell migration, whereas decreased miR-144 expression dramatically enhanced GC cell migration. The met proto-oncogene (MET), which is often amplified in human cancers and functions as an important regulator of cell growth and tumor invasion, was identified as a direct target of miR-144. Moreover, silencing of MET using small interfering RNA (siRNA) recapitulated the anti-metastatic function of miR-144, whereas restoring MET expression attenuated the function of miR-144 in GC cells. Furthermore, we found that miR-144, by targeting MET, suppresses phosphorylation of Akt. Finally, we observed an inverse correlation between the expression of miR-144 and MET mRNA in GC metastatic tissues. In summary, miR-144 suppresses GC progression by directly downregulating MET expression, which subsequently prevents activation of the pro-oncogenic Akt pathway. Reintroduction of miR-144 expression in GC cells presents an attractive therapeutic approach to block the metastasis of gastric cancer.

journal_name

J Exp Clin Cancer Res

journal_title

Journal of experimental & clinical cancer research : CR

authors

Liu J,Xue H,Zhang J,Suo T,Xiang Y,Zhang W,Ma J,Cai D,Gu X

doi

10.1186/s13046-015-0154-5

subject

Has Abstract

pub_date

2015-04-17 00:00:00

pages

35

eissn

0392-9078

issn

1756-9966

pii

10.1186/s13046-015-0154-5

journal_volume

34

pub_type

杂志文章

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