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

Journal of Experimental & Clinical Cancer Research

Xixi Gu³  Dingfang Cai³  Jun Ma³  Wen Zhang³  Yijin Xiang³  Tao Suo¹  Jianjun Zhang²  Hui Xue⁴  Jun Liu³ 

[1]Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, PR China

[2]Department of Oral and Maxillofacial-Head & Neck Oncology, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, PR China

[3]Department of Integrative Medicine, Zhongshan Hospital, Fudan University, Shanghai, PR China

[4]Shanghai University of Traditional Chinese Medicine, School of Basic Medicine, institution of Neijing, Shanghai 201203, China

关键词: Metastases;    Gastric cancer;    MET;    miR-144;    microRNA;   

Others  :  1219938
DOI  :  10.1186/s13046-015-0154-5

 received in 2014-12-21, accepted in 2015-04-03,  发布年份 2015

【 摘 要 】

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.

【 授权许可】

   
2015 Liu et al.; licensee BioMed Central.

【 图 表 】

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