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

被引:717
作者
Hou, Jin [1 ,2 ,3 ]
Lin, Li [4 ]
Zhou, Weiping [5 ]
Wang, Zhengxin [6 ]
Ding, Guoshan [6 ]
Dong, Qiongzhu [7 ,8 ]
Qin, Lunxiu [7 ,8 ]
Wu, Xiaobing [9 ]
Zheng, Yuanyuan [1 ,2 ]
Yang, Yun [5 ]
Tian, Wei [10 ]
Zhang, Qian [1 ,2 ]
Wang, Chunmei [1 ,2 ]
Zhang, Qinghua [1 ,2 ]
Zhuang, Shi-Mei [11 ]
Zheng, Limin [11 ]
Liang, Anmin [12 ]
Tao, Wenzhao [1 ,2 ]
Cao, Xuetao [1 ,3 ]
机构
[1] Second Mil Med Univ, Natl Key Lab Med Immunol, Shanghai 200433, Peoples R China
[2] Second Mil Med Univ, Inst Immunol, Shanghai 200433, Peoples R China
[3] Tsinghua Univ, Sch Med, Inst Immunol, Beijing 100084, Peoples R China
[4] Zhejiang Univ, Sch Med, Inst Immunol, Hangzhou 310058, Zhejiang, Peoples R China
[5] Eastern Hepatobiliary Surg Hosp, Dept Hepat Surg 3, Shanghai 200438, Peoples R China
[6] Shanghai Changzheng Hosp, Dept Organ Transplantat, Shanghai 200003, Peoples R China
[7] Fudan Univ, Liver Canc Inst, Shanghai 200032, Peoples R China
[8] Fudan Univ, Zhongshan Hosp, Inst Biomed Sci, Shanghai 200032, Peoples R China
[9] Natl Lab Mol Virol & Genet Engn, Beijing 100052, Peoples R China
[10] Beijing Genom Inst, Shenzhen 518083, Peoples R China
[11] Sun Yat Sen Univ, Sch Life Sci, Guangzhou 510275, Guangdong, Peoples R China
[12] Guangxi Med Univ, Affiliated Tumor Hosp, Nanning 530021, Peoples R China
基金
中国国家自然科学基金;
关键词
MICRORNA EXPRESSION; I INTERFERON; CANCER; APOPTOSIS; CELLS; MIR-122; INDUCTION; PHENOTYPE; DELIVERY; PATHWAY;
D O I
10.1016/j.ccr.2011.01.001
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 similar to 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.
引用
收藏
页码:232 / 243
页数:12
相关论文
共 45 条
[1]   Phosphatase SHP-1 promotes TLR- and RIG-I-activated production of type I interferon by inhibiting the kinase IRAK1 [J].
An, Huazhang ;
Hou, Jin ;
Zhou, Jun ;
Zhao, Wei ;
Xu, Hongmei ;
Zheng, Yuejuan ;
Yu, Yizhi ;
Liu, Shuxun ;
Cao, Xuetao .
NATURE IMMUNOLOGY, 2008, 9 (05) :542-550
[2]   Identification of the Human Mature B Cell miRNome [J].
Basso, Katia ;
Sumazin, Pavel ;
Morozov, Pavel ;
Schneider, Christof ;
Maute, Roy L. ;
Kitagawa, Yukiko ;
Mandelbaum, Jonathan ;
Haddad, Joseph, Jr. ;
Chen, Chang-Zheng ;
Califano, Andrea ;
Dalla-Favera, Riccardo .
IMMUNITY, 2009, 30 (05) :744-752
[3]   MicroRNA expression profiling: A molecular tool for defining, the phenotype of hepatocellular tumors [J].
Braconi, Chiara ;
Patel, Tushar .
HEPATOLOGY, 2008, 47 (06) :1807-1809
[4]   Endogenous microRNA can be broadly exploited to regulate transgene expression according to tissue, lineage and differentiation state [J].
Brown, Brian D. ;
Gentner, Bernhard ;
Cantore, Alessio ;
Colleoni, Silvia ;
Amendola, Mario ;
Zingale, Anna ;
Baccarini, Alessia ;
Lazzari, Giovanna ;
Galli, Cesare ;
Naldini, Luigi .
NATURE BIOTECHNOLOGY, 2007, 25 (12) :1457-1467
[5]   Pak4 induces premature senescence via a pathway requiring p16INK4/P19ARF and mitogen-activated protein kinase signaling [J].
Cammarano, MS ;
Nekrasova, T ;
Noel, B ;
Minden, A .
MOLECULAR AND CELLULAR BIOLOGY, 2005, 25 (21) :9532-9542
[6]   Loss of miR-122 expression in liver cancer correlates with suppression of the hepatic phenotype and gain of metastatic properties [J].
Coulouarn, C. ;
Factor, V. M. ;
Andersen, J. B. ;
Durkin, M. E. ;
Thorgeirsson, S. S. .
ONCOGENE, 2009, 28 (40) :3526-3536
[7]   Meta-analysis of small RNA-sequencing errors reveals ubiquitous post-transcriptional RNA modifications [J].
Ebhardt, H. Alexander ;
Tsang, Herbert H. ;
Dai, Denny C. ;
Liu, Yifeng ;
Bostan, Babak ;
Fahlman, Richard P. .
NUCLEIC ACIDS RESEARCH, 2009, 37 (08) :2461-2470
[8]   Molecular origins of cancer: Epigenetics in cancer [J].
Esteller, Manel .
NEW ENGLAND JOURNAL OF MEDICINE, 2008, 358 (11) :1148-1159
[9]   Targeting group II PAKs in cancer and metastasis [J].
Eswaran, Jeyanthy ;
Soundararajan, Meera ;
Knapp, Stefan .
CANCER AND METASTASIS REVIEWS, 2009, 28 (1-2) :209-217
[10]   MiR-199a-3p Regulates mTOR and c-Met to Influence the Doxorubicin Sensitivity of Human Hepatocarcinoma Cells [J].
Fornari, Francesca ;
Milazzo, Maddalena ;
Chieco, Pasquale ;
Negrini, Massimo ;
Calin, George Adrian ;
Grazi, Gian Luca ;
Pollutri, Daniela ;
Croce, Carlo Maria ;
Bolondi, Luigi ;
Gramantieri, Laura .
CANCER RESEARCH, 2010, 70 (12) :5184-5193