MicroRNA-128 downregulates Bax and induces apoptosis in human embryonic kidney cells

被引:65
作者
Adlakha, Yogita K. [1 ]
Saini, Neeru [1 ]
机构
[1] Council Sci & Ind Res CSIR, Funct Genom Unit, Inst Genom & Integrat Biol, Delhi 110007, India
关键词
miRNA; Apoptosis; Bax; Reactive oxygen species; Mitochondrial membrane potential; LUNG-CANCER; EXPRESSION; INHIBITION; PREDICTION; REVEALS; MIRNA;
D O I
10.1007/s00018-010-0528-y
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
MicroRNAs (miRNAs) are short similar to 21-nt non-coding RNA molecules that have been shown to regulate a number of biological processes. Previous reports have shown that overexpression of miR-128 in glioma cells inhibited cell proliferation. Literature also suggests that miR-128 negatively regulates prostate cancer cell invasion. Here, we show that overexpression of hsa-miR-128, a brain-enriched microRNA, induces apoptosis in HEK293T cells as elucidated by apoptosis assay, cell cycle changes, loss of mitochondrial membrane potential and multicaspase assay. By in silico analysis, we identified a putative target site within the 3' untranslated region (UTR) of Bax, a proapoptotic member of the apoptosis pathway. We found that ectopic expression of hsa-miR-128 suppressed a luciferase reporter containing the Bax-3' UTR and reduced the levels of Bax in HEK293T cells. Taken together, our study demonstrates that overexpression of hsa-miR-128 not only induces apoptosis in HEK293T cells but also is an endogenous regulator of Bax protein.
引用
收藏
页码:1415 / 1428
页数:14
相关论文
共 34 条
  • [1] Antimitochondrial agents:: a new class of anticancer agents
    André, N
    Rome, A
    Carré, M
    [J]. ARCHIVES DE PEDIATRIE, 2006, 13 (01): : 69 - 75
  • [2] ANDREAS G, 2003, INTRO APOPTOSIS APOR, P1
  • [3] Disruption of mitochondrial membrane potential during apoptosis induced by PSC 833 and CsA in multidrug-resistant lymphoid leukemia
    Bustamante, J
    Lopes, EC
    Garcia, M
    Di Libero, E
    Alvarez, E
    Hajos, SE
    [J]. TOXICOLOGY AND APPLIED PHARMACOLOGY, 2004, 199 (01) : 44 - 51
  • [4] MicroRNAs modulate hematopoietic lineage differentiation
    Chen, CZ
    Li, L
    Lodish, HF
    Bartel, DP
    [J]. SCIENCE, 2004, 303 (5654) : 83 - 86
  • [5] Antisense inhibition of human miRNAs and indications for an involvement of miRNA in cell growth and apoptosis
    Cheng, AM
    Byrom, MW
    Shelton, J
    Ford, LP
    [J]. NUCLEIC ACIDS RESEARCH, 2005, 33 (04) : 1290 - 1297
  • [6] 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
  • [7] The BCL2 family: Regulators of the cellular life-or-death switch
    Cory, S
    Adams, JM
    [J]. NATURE REVIEWS CANCER, 2002, 2 (09) : 647 - 656
  • [8] Micro-RNA-128 (miRNA-128) down-regulation in glioblastoma targets ARP5 (ANGPTL6), Bmi-1 and E2F-3a, key regulators of brain cell proliferation
    Cui, J. G.
    Zhao, Y.
    Sethi, P.
    Li, Y. Y.
    Mahta, A.
    Culicchia, F.
    Lukiw, W. J.
    [J]. JOURNAL OF NEURO-ONCOLOGY, 2010, 98 (03) : 297 - 304
  • [9] MiR-128 up-regulation inhibits Reelin and DCX expression and reduces neuroblastoma cell motility and invasiveness
    Evangelisti, Cristina
    Florian, Maria Carolina
    Massimi, Isabella
    Dominici, Carlo
    Giannini, Giuseppe
    Galardi, Silvia
    Bue, Maria Cristina
    Massalini, Simone
    McDowell, Heather P.
    Messi, Elio
    Gulino, Alberto
    Farace, Maria Giulia
    Ciafre, Silvia Anna
    [J]. FASEB JOURNAL, 2009, 23 (12) : 4276 - 4287
  • [10] MicroRNAs in Cancer
    Lee, Yong Sun
    Dutta, Anindya
    [J]. ANNUAL REVIEW OF PATHOLOGY-MECHANISMS OF DISEASE, 2009, 4 : 199 - 227