|
|
|
| MicroRNA-449a suppresses hepatocellular carcinoma cell growth via G1 phase arrest and the HGF/MET c-Met pathway |
| Jun Cheng a , Li-Ming Wu b , c , Xue-Song Deng a , Jian Wu b , c , Zhen Lv b , c , Hang-Fen Zhao a , Zhang Yang d , e , Yong Ni a , * |
a Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital, Shenzhen 518035, China
b Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
c Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Hangzhou 310003, China
d Institutes of Biomedical Sciences, Fudan University, Shanghai 20 0 032, China
e School of Life Science, Fudan University, Shanghai 200433, China
∗ Corresponding author.
E-mail address: szniyong@sina.com (Y. Ni). |
|
|
|
|
Abstract BACKGROUND:
Accumulating evidence demonstrates that microRNAs (miRNAs) play essential roles in tumorigenesis and cancer progression of hepatocellular carcinoma (HCC). Average targets of a miRNA were more than 100. And one miRNA may act in tumor via regulating several targets. The present study aimed to explore more potential targets of miR-449a by proteomics technology and further uncover the role of miR-449a in HCC tumorigenesis.
METHODS:
Technologies such as iTRAQ-based quantitative proteomic were used to investigate the effect of miR-449a on HCC. The expression of c-Met and miR-449a was detected by qRT-PCR in HCC samples. Gain- and loss-of-function experiments were performed to identify the function and potential target of miR-449a in HCC cells.
RESULTS:
In HCC, miR-449a was significantly downregulated, while c-Met was upregulated concurrently. Quantitative proteomics and luciferase reporter assay identified c-Met as a direct target of miR-449a. Moreover, miR-449a inhibited HCC growth not only by targeting CDK6 but also by suppressing c-Met/Ras/Raf/ERK signaling pathway. Furthermore, the inhibition of c-Met expression with a specific siRNA significantly inhibited cells growth and deregulated the ERK pathway in HCC.
CONCLUSION:
The tumor suppressor miR-449a suppresses HCC tumorigenesis by repressing the c-Met/ERK pathway.
|
|
|
|
|
|
|
|
|
2018, Vol. 17 
