title: MiR-139 inhibits Mcl-1 expression and potentiates TMZ-induced apoptosis in glioma.
abstract: OBJECTIVE
  Mcl-1, an antiapoptotic member of the Bcl-2 family, is overexpressed in human glioblastoma, conferring a survival advantage to tumor cells. The mechanisms underlying its dysregulation have not been clarified. In this study, we explored the involvement of micro-RNAs that acted as endogenous sequence-specific suppressors of gene expression.
  
  
  RESULTS
  Using computational and TCGA analysis, we identified miR-139 as being downregulated in glioblastoma in comparison with human brain tissue, as well as possessing a putative target site in Mcl-1 mRNA. Overexpression of miR-139 led to a clear decrease in Mcl-1 expression in gliomas. Reporter assays revealed direct post-transcriptional regulation involving miR-139 and the 3'-untranslated region of Mcl-1. Human glioma tissues with low expression of miR-139 displayed higher expression of Mcl-1 protein than those with high expression, suggesting that low miR-139 contributes to Mcl-1 overexpression. In addition, upregulation of miR-139 suppressed the proliferation and enhanced temozolomide (TMZ)-induced apoptosis. Finally, we observed that Mcl-1 knockdown resulted in similar effects compared with miR-139 transfection.
  
  
  CONCLUSIONS
  Our results suggested that miR-139 negatively regulated Mcl-1 and induced apoptosis in cooperation with an anticancer drug TMZ in glioma.
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Rui-Yan
authors.initials: RY
authors.lastname: Li
authors.forename: Ling-Chao
authors.initials: LC
authors.lastname: Chen
authors.forename: Hai-Yan
authors.initials: HY
authors.lastname: Zhang
authors.forename: Wen-Zhong
authors.initials: WZ
authors.lastname: Du
authors.forename: Yan
authors.initials: Y
authors.lastname: Feng
authors.forename: Han-Bing
authors.initials: HB
authors.lastname: Wang
authors.forename: Jin-Qiong
authors.initials: JQ
authors.lastname: Wen
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.forename: Xian-Feng
authors.initials: XF
authors.lastname: Li
authors.forename: Ying
authors.initials: Y
authors.lastname: Sun
authors.forename: Dong-Bo
authors.initials: DB
authors.lastname: Yang
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
authors.forename: Yong-Li
authors.initials: YL
authors.lastname: Li
authors.forename: Chuan-Lu
authors.initials: CL
authors.lastname: Jiang
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D005910:Glioma / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D008156:Luciferases / Q000235:genetics; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000378:metabolism / Q000494:pharmacology*; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000096:biosynthesis*; D009368:Neoplasm Transplantation; D009841:Oligonucleotides / Q000235:genetics; D016612:Paraffin Embedding; D010957:Plasmids / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D000077204:Temozolomide
chemical_list: D020413:3' Untranslated Regions; D018906:Antineoplastic Agents, Alkylating; C546202:MIRN139 microRNA, mouse; C579094:Mcl1 protein, mouse; D035683:MicroRNAs; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009841:Oligonucleotides; D003606:Dacarbazine; D008156:Luciferases; D000077204:Temozolomide
references.citation: Clin Cancer Res. 2007 Apr 1;13(7):2144-50
references.pmid: 17404098
references.citation: Oncol Rep. 2012 Mar;27(3):854-60
references.pmid: 22075712
references.citation: Proc Natl Acad Sci U S A. 2007 Dec 4;104(49):19512-7
references.pmid: 18040043
references.citation: Neuro Oncol. 2011 Nov;13(11):1202-12
references.pmid: 21846680
references.citation: PLoS One. 2012;7(6):e38096
references.pmid: 22723849
references.citation: Biochem Biophys Res Commun. 2009 Dec 25;390(4):1278-82
references.pmid: 19883627
references.citation: Cell Biochem Funct. 2013 Jun;31(4):319-24
references.pmid: 23001723
references.citation: Oncol Rep. 2010 Jul;24(1):65-72
references.pmid: 20514445
references.citation: Nat Rev Cancer. 2006 Nov;6(11):857-66
references.pmid: 17060945
references.citation: Genes Cancer. 2010 Apr 1;1(4):381-387
references.pmid: 20657750
references.citation: Oncogene. 2009 Jul 30;28(30):2738-44
references.pmid: 19503096
references.citation: Mol Pharm. 2011 Aug 1;8(4):1381-9
references.pmid: 21648427
references.citation: Blood. 2008 Jun 1;111(11):5350-8
references.pmid: 18292288
references.citation: Eur J Cancer. 2012 Nov;48(16):3104-11
references.pmid: 22406049
references.citation: Biochem Biophys Res Commun. 2002 Feb 1;290(4):1275-81
references.pmid: 11812001
references.citation: Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2008 Oct;25(5):497-501
references.pmid: 18841558
references.citation: Science. 2008 Sep 26;321(5897):1807-12
references.pmid: 18772396
references.citation: J Biomater Sci Polym Ed. 2010;21(3):303-14
references.pmid: 20178687
references.citation: Expert Opin Ther Targets. 2010 Nov;14(11):1247-57
references.pmid: 20942748
references.citation: Cancer Res. 2011 May 15;71(10):3563-72
references.pmid: 21471404
references.citation: Biochem Pharmacol. 2012 Aug 1;84(3):320-30
references.pmid: 22580051
references.citation: Zhonghua Zhong Liu Za Zhi. 2011 Oct;33(10):747-51
references.pmid: 22335906
references.citation: Cancer Res. 2009 Feb 1;69(3):1135-42
references.pmid: 19155302
references.citation: Oncol Rep. 2010 Jul;24(1):195-201
references.pmid: 20514462
references.citation: J Transl Med. 2012 Jun 08;10:119
references.pmid: 22681957
references.citation: Int J Oncol. 2009 Jun;34(6):1653-60
references.pmid: 19424584
references.citation: Int J Oncol. 2010 Apr;36(4):913-20
references.pmid: 20198336
references.citation: Cancer Res. 2006 Jul 1;66(13):6589-97
references.pmid: 16818631
references.citation: Neuro Oncol. 2012 Aug;14(8):1026-36
references.pmid: 22649212
references.citation: Int J Biochem Cell Biol. 2012 Sep;44(9):1465-72
references.pmid: 22642900
references.citation: J Hepatol. 2006 Jan;44(1):151-7
references.pmid: 16289418
references.citation: Clin Cancer Res. 2010 Feb 1;16(3):957-66
references.pmid: 20103677
references.citation: Genomics Proteomics Bioinformatics. 2009 Dec;7(4):147-54
references.pmid: 20172487
references.citation: Biochem Biophys Res Commun. 2009 Oct 23;388(3):483-9
references.pmid: 19654003
references.citation: Am J Pathol. 2010 Jul;177(1):29-38
references.pmid: 20472885