Identification of miRNomes in Human Liver and Hepatocellular Carcinoma Reveals miR-199a/b-3p as Therapeutic Target for Hepatocellular Carcinoma

• Published in: Cancer cell Vol. 19; no. 2; pp. 232 - 243
• Main Authors: Hou, Jin, Lin, Li, Zhou, Weiping, Wang, Zhengxin, Ding, Guoshan, Dong, Qiongzhu, Qin, Lunxiu, Wu, Xiaobing, Zheng, Yuanyuan, Yang, Yun, Tian, Wei, Zhang, Qian, Wang, Chunmei, Zhang, Qinghua, Zhuang, Shi-Mei, Zheng, Limin, Liang, Anmin, Tao, Wenzhao, Cao, Xuetao
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.02.2011
• Subjects: Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - metabolism; Carcinoma, Hepatocellular - therapy; DNA Methylation; Hepatitis B - genetics; Hepatitis C - genetics; Humans; Liver - metabolism; Liver Neoplasms - genetics; Liver Neoplasms - metabolism; Liver Neoplasms - therapy; MicroRNAs - genetics; Reverse Transcriptase Polymerase Chain Reaction; Survival Analysis
• ISSN: 1535-6108; 1878-3686
• DOI: 10.1016/j.ccr.2011.01.001

The full scale of human miRNome in specific cell or tissue, especially in cancers, remains to be determined. An in-depth analysis of miRNomes in human normal liver, hepatitis liver, and hepatocellular carcinoma (HCC) was carried out in this study. We found nine miRNAs accounted for ∼88.2% of the miRNome in human liver. The third most highly expressed miR-199a/b-3p is consistently decreased in HCC, and its decrement significantly correlates with poor survival of HCC patients. Moreover, miR-199a/b-3p can target tumor-promoting PAK4 to suppress HCC growth through inhibiting PAK4/Raf/MEK/ERK pathway both in vitro and in vivo. Our study provides miRNomes of human liver and HCC and contributes to better understanding of the important deregulated miRNAs in HCC and liver diseases. ► Identification of miRNomes in human normal liver, hepatitis liver and HCC ► miR-199a/b-3p is the most consistently decreased miRNA in HCC ► Low miR-199-3p expression correlates with poor survival of HCC patients ► miR-199-3p inhibits PAK4/Raf/MEK/ERK prosurvival pathway in HCC