title: miR-340 suppresses glioblastoma multiforme.
abstract: Deregulation of microRNAs (miRs) contributes to tumorigenesis. Down-regulation of miR-340 is observed in multiple types of cancers. However, the biological function of miR-340 in glioblastoma multiforme (GBM) remains largely unknown. In the present study, we demonstrated that expression of miR-340 was downregulated in both glioma cell lines and tissues. Survival of GBM patients with high levels of miR-340 was significantly extended in comparison to patients expressing low miR-340 levels. Biological functional experiments showed that the restoration of miR-340 dramatically inhibited glioma cell proliferation, induced cell-cycle arrest and apoptosis, suppressed cell motility and promoted autophagy and terminal differentiation. Mechanistic studies disclosed that, miR-340 over-expression suppressed several oncogenes including p-AKT, EZH2, EGFR, BMI1 and XIAP. Furthermore, ROCK1 was validated as a direct functional target miR-340 and silencing of ROCK1 phenocopied the anti-tumor effect of mR-340. Our findings indicate an important role of miR-340 as a glioma killer, and suggest a potential prognosis biomarker and therapeutic target for GBM.
authors.affiliation: Department of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.|Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Daquan
authors.initials: D
authors.lastname: Huang
authors.affiliation: Department of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Shuwei
authors.initials: S
authors.lastname: Qiu
authors.affiliation: Key Laboratory of Gene Engineering of the Ministry of Education and State Key Laboratory of Biocontrol, College of Life Sciences, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Ruiguang
authors.initials: R
authors.lastname: Ge
authors.affiliation: Department of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Lei
authors.initials: L
authors.lastname: He
authors.affiliation: Department of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.|Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Peng
mesh_terms: D017209:Apoptosis / Q000235:genetics; D001343:Autophagy / Q000235:genetics; D001932:Brain Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D059447:Cell Cycle Checkpoints / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D015536:Down-Regulation; D000071221:Enhancer of Zeste Homolog 2 Protein; D066246:ErbB Receptors / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D063150:Polycomb Repressive Complex 1 / Q000378:metabolism; D063151:Polycomb Repressive Complex 2 / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000378:metabolism; D054460:rho-Associated Kinases / Q000096:biosynthesis / Q000235:genetics*
chemical_list: C069077:BMI1 protein, human; C570046:MIRN340 microRNA, human; D035683:MicroRNAs; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2; D063150:Polycomb Repressive Complex 1; C512478:EGFR protein, human; D066246:ErbB Receptors; D051057:Proto-Oncogene Proteins c-akt; C515851:ROCK1 protein, human; D054460:rho-Associated Kinases
keywords: ROCK1; biomarker; glioblastoma multiforme; miR-340
references.citation: Proc Natl Acad Sci U S A. 2007 Aug 14;104(33):13438-43
references.pmid: 17679696
references.citation: Glia. 2009 Apr 1;57(5):499-509
references.pmid: 18814230
references.citation: EMBO J. 2011 Nov 16;30(22):4628-41
references.pmid: 21915098
references.citation: EMBO J. 2013 Aug 14;32(16):2204-16
references.pmid: 23749209
references.citation: Cancer Res. 2009 Dec 15;69(24):9211-8
references.pmid: 19934320
references.citation: J Transl Med. 2013;11:10
references.pmid: 23302469
references.citation: Curr Med Chem. 2013;20(15):1974-84
references.pmid: 23317162
references.citation: Biochem Biophys Res Commun. 2013 Aug 9;437(4):653-8
references.pmid: 23872151
references.citation: Clin Cancer Res. 2010 May 15;16(10):2715-28
references.pmid: 20442299
references.citation: Cancer Res. 2008 Nov 15;68(22):9125-30
references.pmid: 19010882
references.citation: PLoS One. 2009;4(12):e8190
references.pmid: 19997641
references.citation: Nat Rev Mol Cell Biol. 2003 Jun;4(6):446-56
references.pmid: 12778124
references.citation: BMC Syst Biol. 2010;4:163
references.pmid: 21114830
references.citation: Cancer Res. 2012 Oct 15;72(20):5338-47
references.pmid: 22942252
references.citation: Genes Cancer. 2013 Jul;4(7-8):285-96
references.pmid: 24167656
references.citation: Nature. 2006 Dec 7;444(7120):761-5
references.pmid: 17151667
references.citation: N Engl J Med. 2008 Jul 31;359(5):492-507
references.pmid: 18669428
references.citation: Mol Cell. 2003 Feb;11(2):519-27
references.pmid: 12620238
references.citation: Genes Cancer. 2012 Jan;3(1):3-15
references.pmid: 22893786
references.citation: Cell. 2001 Mar 9;104(5):769-80
references.pmid: 11257230
references.citation: Differentiation. 2010 Feb;79(2):84-92
references.pmid: 19889495
references.citation: Int J Cancer. 2011 Dec 1;129(11):2720-31
references.pmid: 21384342
references.citation: Cell. 2001 Mar 9;104(5):791-800
references.pmid: 11257232
references.citation: J Biol Chem. 2004 Mar 26;279(13):13205-14
references.pmid: 14726536
references.citation: Mol Cancer Ther. 2014 Apr;13(4):976-85
references.pmid: 24448820
references.citation: Cancer Cell. 2008 Jan;13(1):69-80
references.pmid: 18167341
references.citation: Oncogene. 2015 Jun;34(25):3240-50
references.pmid: 25151966
references.citation: Brain. 2011 Dec;134(Pt 12):3578-89
references.pmid: 22088562
references.citation: Cancer Cell. 2011 Jun 14;19(6):776-91
references.pmid: 21665151
references.citation: Cell. 2004 Jan 23;116(2):281-97
references.pmid: 14744438
references.citation: Oncogene. 2010 Feb 18;29(7):937-48
references.pmid: 19935707
references.citation: Gene Ther. 2007 Jan;14(2):147-61
references.pmid: 16957768
references.citation: Biochim Biophys Acta. 2013 Oct;1832(10):1697-707
references.pmid: 23707559
references.citation: Cell Tissue Res. 2015 Jan;359(1):225-54
references.pmid: 25416506
references.citation: J Mol Histol. 2014 Dec;45(6):707-14
references.pmid: 25178638
references.citation: JAMA. 2013 Nov 6;310(17):1842-50
references.pmid: 24193082
references.citation: Cancer Res. 2007 Mar 15;67(6):2456-68
references.pmid: 17363563
references.citation: J Neurosci. 2009 Jul 15;29(28):8884-96
references.pmid: 19605626
references.citation: Oncotarget. 2014 Aug 30;5(16):6687-700
references.pmid: 25149532
references.citation: Cancer Cell. 2007 Oct;12(4):328-41
references.pmid: 17936558
references.citation: Oncogene. 2013 Jun 13;32(24):2927-36
references.pmid: 22797059
references.citation: CA Cancer J Clin. 2010 May-Jun;60(3):166-93
references.pmid: 20445000
references.citation: Nat Commun. 2013;4:2189
references.pmid: 23877263
references.citation: Cancer. 2011 Jul 1;117(13):2842-52
references.pmid: 21692045
references.citation: Oncol Rep. 2012 Oct;28(4):1346-52
references.pmid: 22895557
references.citation: Hepatogastroenterology. 2012 Nov-Dec;59(120):2523-6
references.pmid: 22584506
references.citation: Am J Pathol. 2010 Feb;176(2):699-709
references.pmid: 20035051
references.citation: Br J Cancer. 2007;96 Suppl:R40-4
references.pmid: 17393584
references.citation: EMBO J. 2012 Jan 18;31(2):481-93
references.pmid: 22085929