MicroRNA-362-5p promotes tumor growth and metastasis by targeting CYLD in hepatocellular carcinoma. Issue 2 (28th January 2015)

• Record Type: Journal Article
• Authors: Ni, Fang; Zhao, Hua; Cui, Huaqin; Wu, Zhengsheng; Chen, Li; Hu, Zhongqian; Guo, Chuang; Liu, Yakun; Chen, Zhuo; Wang, Xinyi; Chen, Danlei; Wei, Haiming; Wang, Siying
• Is Part Of: Cancer letters. Volume 356:Issue 2(2015)Part B
• Page Start: 809
• Page End: 818
• Publication Date: 2015-01-28
• Subjects: miRNA microRNA -- HCC hepatocellular carcinoma -- mRNA messenger RNA -- UTR untranslated region -- BCA bicinchoninic acid -- siRNA small interfering RNA -- qRT-PCR quantitative reverse transcription PCR -- NF-κB nuclear factor κB.; miR-362-5p -- Hepatocellular carcinoma -- Metastasis -- CYLD; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2014.10.041
• Languages: English
• ISSNs: 0304-3835

Abstract

Highlights: MiR-362-5p is frequently up-regulated in hepatocellular carcinoma (HCC) and associated with HCC progression. Inhibition of miR-362-5p significantly decreases HCC cell proliferation, clonogenicity, migration, and invasion in vitro . Inhibition of miR-362-5p dramatically suppresses HCC tumor growth and metastasis in vivo . MiR-362-5p targets CYLD through its 3′-UTR in HCC cells. MiR-362-5p acts through CYLD to activate the NF-κB signaling pathway, which contributes to HCC progression. Abstract: MicroRNAs are increasingly recognized as playing important roles in hepatocellular carcinoma (HCC) tumorigenesis. Here we identified an essential role for miR-362-5p in the regulation of HCC development. We found that miR-362-5p was significantly up-regulated in HCCs and associated with HCC progression. Inhibition of miR-362-5p in HCC cells dramatically decreased cell proliferation, clonogenicity, migration and invasion in vitro as well as tumor growth and metastasis in vivo . We subsequently identified that CYLD was a target gene of miR-362-5p. Furthermore, knockdown of CYLD expression partially counteracted the tumor suppressive effects of miR-362-5p inhibitors. Finally, we have shown that miR-362-5p acts through CYLD to activate the NF-κB signaling pathway, which contributes to HCC progression. Taken together, our findings indicate that miR-362-5p belongs to a new class of oncomiR that regulates HCC cell aggressiveness, thus providing new insight into the molecular mechanisms underlying HCC development. This study also suggests that miR-362-5p may serve as a novel therapeutic target for miRNA based HCC therapy.