Cyclin g1 is a target of miR-122a, a MicroRNA frequently down-regulated in human hepatocellular carcinoma

被引:689
作者
Gramantieri, Laura
Ferracin, Manuela
Fornari, Francesca
Veronese, Airtgelo
Sabbioni, Silvia
Liu, Chang-Gong
Calin, George A.
Giovannini, Catia
Ferrazzi, Eros
Grazi, Gian Luca
Croce, Carlo M.
Bolondi, Luigi
Negrini, Massimo
机构
[1] Univ Bologna, Dipartimento Med Interna & Gastroenterol, I-40126 Bologna, Italy
[2] Univ Bologna, Ctr Ricerca Biomed Apolicata, I-40126 Bologna, Italy
[3] Univ Ferrara, Deipartimeno Med Sperimentale & Diagnost, I-44100 Ferrara, Italy
[4] Univ Ferrara, Comprehens Canc Ctr, I-44100 Ferrara, Italy
[5] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH USA
[6] Ist Oncol Veneto, Rovigo, Italy
关键词
D O I
10.1158/0008-5472.CAN-06-4607
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
We investigated the role of microRNAs (miRNAs) in the pathogenesis of human hepatocellular carcinoma (HCC). A genome-wide miRNA microarray was used to identify differentially expressed miRNAs in HCCs arisen on cirrhotic livers. Thirty-five miRNAs were identified. Several of these miRNAs were previously found deregulated in other human cancers, such as members of the let-7 family, mir-221, and mir-145. In addition, the hepato-specific miR-122a was found down-regulated in similar to 70% of HCCs and in all HCC-derived cell lines. Microarray data for let-7a, mir-221, and mir-122a were validated by Northern blot and real-time PCR analysis. Understanding the contribution of deregulated miPNAs to cancer requires the identification of gene targets. Here, we show that miR-122a can modulate cyclin G1 expression in HCC-derived cell lines and an inverse correlation between miR-122a and cyclin G1 expression exists in primary liver carcinomas. These results indicate that cyclin G1 is a target of miR-122a and expand our knowledge of the molecular alterations involved in HCC pathogenesis and of the role of miRNAs in human cancer.
引用
收藏
页码:6092 / 6099
页数:8
相关论文
共 51 条
  • [1] The functions of animal microRNAs
    Ambros, V
    [J]. NATURE, 2004, 431 (7006) : 350 - 355
  • [2] Increased expression of cyclin G1 in leiomyoma compared with normal myometrium
    Baek, WK
    Kim, D
    Jung, N
    Yi, YW
    Kim, JM
    Cha, SD
    Bae, I
    Cho, CH
    [J]. AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY, 2003, 188 (03) : 634 - 639
  • [3] Identification by Real-time PCR of 13 mature microRNAs differentially expressed in colorectal cancer and non-tumoral tissues
    Bandres, E.
    Cubedo, E.
    Agirre, X.
    Malumbres, R.
    Zarate, R.
    Ramirez, N.
    Abajo, A.
    Navarro, A.
    Moreno, I.
    Monzo, M.
    Garcia-Foncillas, J.
    [J]. MOLECULAR CANCER, 2006, 5 (1)
  • [4] Identification of hundreds of conserved and nonconserved human microRNAs
    Bentwich, I
    Avniel, A
    Karov, Y
    Aharonov, R
    Gilad, S
    Barad, O
    Barzilai, A
    Einat, P
    Einav, U
    Meiri, E
    Sharon, E
    Spector, Y
    Bentwich, Z
    [J]. NATURE GENETICS, 2005, 37 (07) : 766 - 770
  • [5] A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia
    Calin, GA
    Ferracin, M
    Cimmino, A
    Di Leva, G
    Shimizu, M
    Wojcik, SE
    Iorio, MV
    Visone, R
    Sever, NI
    Fabbri, M
    Iuliano, R
    Palumbo, T
    Pichiorri, F
    Roldo, C
    Garzon, R
    Sevignani, C
    Rassenti, L
    Alder, H
    Volinia, S
    Liu, CG
    Kipps, TJ
    Negrini, M
    Croce, CM
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 2005, 353 (17) : 1793 - 1801
  • [6] MicroRNA profiling reveals distinct signatures in B cell chronic lymphocytic leukemias
    Calin, GA
    Liu, CG
    Sevignani, C
    Ferracin, M
    Felli, N
    Dumitru, CD
    Shimizu, M
    Cimmino, A
    Zupo, S
    Dono, M
    Dell'Aquila, ML
    Alder, H
    Rassenti, L
    Kipps, TJ
    Bullrich, F
    Negrini, M
    Croce, CM
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (32) : 11755 - 11760
  • [7] Retroviral vector-mediated transfer of an antisense cyclin G1 construct inhibits osteosarcoma tumor growth in nude mice
    Chen, DS
    Zhu, NL
    Hung, G
    Skotzko, MJ
    Hinton, DR
    Tolo, V
    Hall, FL
    Anderson, WF
    Gordon, EM
    [J]. HUMAN GENE THERAPY, 1997, 8 (14) : 1667 - 1674
  • [8] Extensive modulation of a set of microRNAs in primary glioblastoma
    Ciafrè, SA
    Galardi, S
    Mangiola, A
    Ferracin, M
    Liu, CG
    Sabatino, G
    Negrini, M
    Maira, G
    Croce, CM
    Farace, MG
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2005, 334 (04) : 1351 - 1358
  • [9] miR-15 and miR-16 induce apoptosis by targeting BCL2
    Cimmino, A
    Calin, GA
    Fabbri, M
    Iorio, MV
    Ferracin, M
    Shimizu, M
    Wojcik, SE
    Aqeilan, RI
    Zupo, S
    Dono, M
    Rassenti, L
    Alder, H
    Volinia, S
    Liu, CG
    Kipps, TJ
    Negrini, M
    Croce, CM
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (39) : 13944 - 13949
  • [10] The colorectal microRNAome
    Cummins, JM
    He, YP
    Leary, RJ
    Pagliarini, R
    Diaz, LA
    Sjoblom, T
    Barad, O
    Bentwich, Z
    Szafranska, AE
    Labourier, E
    Raymond, CK
    Roberts, BS
    Juhl, H
    Kinzler, KW
    Vogelstein, B
    Velculescu, VE
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (10) : 3687 - 3692