MicroRNA-26a regulates tumorigenic properties of EZH2 in human lung carcinoma cells

被引:90
作者
Dang, Xiaomin [2 ]
Ma, Aiqun [1 ]
Yang, Lan [2 ]
Hu, Hao [3 ]
Zhu, Bo [2 ]
Shang, Dong [2 ]
Chen, Tianjun [2 ]
Luo, Yu [4 ]
机构
[1] Xi An Jiao Tong Univ, Affiliated Hosp 1, Dept Cardiol, Xian 710061, Shaanxi Provinc, Peoples R China
[2] Xi An Jiao Tong Univ, Affiliated Hosp 1, Dept Respirat, Xian 710061, Shaanxi Provinc, Peoples R China
[3] Xi An Jiao Tong Univ, Dept Pharmacol, Xian 710061, Shaanxi Provinc, Peoples R China
[4] Xi An Jiao Tong Univ, Dept Med Ctr, Xian 710061, Shaanxi Provinc, Peoples R China
关键词
MicroRNA-26a; human lung cancer; EZH2; DAB2IP; RUNX3; POLYCOMB GROUP GENE; GROUP PROTEIN EZH2; PROSTATE-CANCER; HISTONE METHYLTRANSFERASE; INCREASED EXPRESSION; EPITHELIAL-CELLS; STEM-CELLS; MIR-26A; RUNX3; DIFFERENTIATION;
D O I
10.1016/j.cancergen.2012.01.002
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
MicroRNAs (miRNAs) are a class of 21-23 nucleotide RNA molecules that play critical roles in the regulation of various cancers, including human lung cancer. Among them, miR-26a has been identified as a tumor-related regulator in several cancers, but its pathophysiologic properties and correlation with the development of human lung cancer remain unclear. In this study, it was determined that miR-26a expression is clearly down-regulated in human lung cancer tissues relative to normal tissues. Meanwhile, the overexpression of miR-26a in the A549 human lung cancer cell line dramatically inhibited cell proliferation, blocked G1/S phase transition, induced apoptosis, and inhibited cell metastasis and invasion in vitro. In contrast, a miR-26a inhibitor was used to transfect A549 cells, and the inhibition of endogenous miR-26a promoted cell metastasis and invasion. In addition, miR-26a expression inhibited the expression of enhancer of zeste homolog 2 (EZH2) and transactivated downstream target genes, including disabled homolog 2 (Drosophila) interacting protein gene (DAB2IP) and human Runt-related transcription factor 3 (RUNX3), which suggests that EZH2 is a potential target of miR-26a as previously reported. In conclusion, miR-26a plays an important role as an anti-oncogene in the molecular mechanism of human lung cancer and could potentially be used for the treatment of lung cancer.
引用
收藏
页码:113 / 123
页数:11
相关论文
共 52 条
  • [1] Akao Y, 2006, ONCOL REP, V16, P845
  • [2] miRNA control of tumor cell invasion and metastasis
    Baranwal, Somesh
    Alahari, Suresh K.
    [J]. INTERNATIONAL JOURNAL OF CANCER, 2010, 126 (06) : 1283 - 1290
  • [3] MicroRNAs: Genomics, biogenesis, mechanism, and function (Reprinted from Cell, vol 116, pg 281-297, 2004)
    Bartel, David P.
    [J]. CELL, 2007, 131 (04) : 11 - 29
  • [4] Batura-Gabryel H, 2005, Rocz Akad Med Bialymst, V50 Suppl 1, P152
  • [5] bantam encodes a developmentally regulated microRNA that controls cell proliferation and regulates the proapoptotic gene hid in Drosophila
    Brennecke, J
    Hipfner, DR
    Stark, A
    Russell, RB
    Cohen, SM
    [J]. CELL, 2003, 113 (01) : 25 - 36
  • [6] Increased expression of the EZH2 polycomb group gene in BMI-1-positive neoplastic cells during bronchial carcinogenesis
    Breuer, RHJ
    Snijders, PJF
    Smit, EF
    Sutedja, TG
    Sewalt, RGAB
    Otte, AP
    van Kemenade, FJ
    Postmus, PE
    Meijer, CJLM
    Raaphorst, FM
    [J]. NEOPLASIA, 2004, 6 (06): : 736 - 743
  • [7] Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers
    Calin, GA
    Sevignani, C
    Dan Dumitru, C
    Hyslop, T
    Noch, E
    Yendamuri, S
    Shimizu, M
    Rattan, S
    Bullrich, F
    Negrini, M
    Croce, CM
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (09) : 2999 - 3004
  • [8] Repression of E-cadherin by the polycomb group protein EZH2 in cancer
    Cao, Q.
    Yu, J.
    Dhanasekaran, S. M.
    Kim, J. H.
    Mani, R-S
    Tomlins, S. A.
    Mehra, R.
    Laxman, B.
    Cao, X.
    Yu, J.
    Kleer, C. G.
    Varambally, S.
    Chinnaiyan, A. M.
    [J]. ONCOGENE, 2008, 27 (58) : 7274 - 7284
  • [9] Oct4/Sox2-regulated miR-302 targets cyclin D1 in human embryonic stem cells
    Card, Deborah A. Greer
    Hebbar, Pratibha B.
    Li, Leping
    Trotter, Kevin W.
    Komatsu, Yoshihiro
    Mishina, Yuji
    Archer, Trevor K.
    [J]. MOLECULAR AND CELLULAR BIOLOGY, 2008, 28 (20) : 6426 - 6438
  • [10] Widespread microRNA repression by Myc contributes to tumorigenesis
    Chang, Tsung-Cheng
    Yu, Duonan
    Lee, Yun-Sil
    Wentzel, Erik A.
    Arking, Dan E.
    West, Kristin M.
    Dang, Chi V.
    Thomas-Tikhonenko, Andrei
    Mendell, Joshua T.
    [J]. NATURE GENETICS, 2008, 40 (01) : 43 - 50