MiR-449a suppresses the epithelial-mesenchymal transition and metastasis of hepatocellular carcinoma by multiple targets

BMC Cancer

Research Article

Feng Yuan¹  Jie Xu²  Xiao-feng Pei³  Bao-xin Liu⁴  Fang Zheng⁵  Shu-peng Chen⁶  Yi-ji Liao⁷ 

[1] Department of Breast Surgery, Hubei Provincial Cancer Hospital, No. 116, Zhuodaoquan South Road, Wuhan, China;Department of Pathology, Guangdong Provincial People’s Hospital, No.107, Zhongshan Er Road, Guangzhou, China;Department of Radiation Oncology, the Fifth Affiliated Hospital, Sun Yat-sen University, No. 57, Meihua East Road, Zhuhai, China;Department of orthopedics, Guangzhou hospital of traditional Chinese medicine, No. 16, Zhuji Road, Guangzhou, China;Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107, Yanjiang West Road, 510120, Guangzhou, China;Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107, Yanjiang West Road, 510120, Guangzhou, China;The State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, No. 651, Dongfeng Road East, Guangzhou, China;The State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, No. 651, Dongfeng Road East, Guangzhou, China;

关键词: MiR-449a;    Epithelial–mesenchymal transition;    Metastasis;    Hepatocellular carcinoma;   

DOI  :  10.1186/s12885-015-1738-3

 received in 2014-11-09, accepted in 2015-10-08,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundIncreasing evidence indicates that Epithelial–mesenchymal transition (EMT) can be regulated by microRNAs (miRNAs). MiR-449a is a liver abundant miRNA. However, the role of miR-449a in the metastasis of hepatocellular carcinoma (HCC) remains largely unknown.MethodsThe expression levels of miR-449a were first examined in HCC cell lines and tumour tissues by real-time PCR. The in vitro and in vivo functional effect and underlying molecular mechanisms of miR-449a were examined further.ResultsIn the present study, we found that miR-449a was significantly decreased in HCC cells and tissues, especially in those with the portal vein tumor thrombus. In HCC cell lines, stable overexpression of miR-449a was sufficient to inhibit cell motility in vitro, and pulmonary metastasis in vivo. In addition, ectopic overexpression of miR-449a in HCC cells promoted the expression of epithelial markers and reduced the levels of mesenchymal markers. Further studies revealed that the reintroduction of miR-449a attenuated the downstream signaling of Met, and consequently reduced the accumulation of Snail in cell nucleus by targeting the 3’-untranslated regions (3’-UTR) of FOS and Met.ConclusionsOur data highlight an important role of miR-449a in the molecular etiology of HCC, and implicate the potential application of miR-449a in cancer therapy.

【 授权许可】

CC BY   
© Chen et al. 2015