title: MicroRNA-141 inhibits tumor growth and metastasis in gastric cancer by directly targeting transcriptional co-activator with PDZ-binding motif, TAZ.
abstract: Gastric cancer (GC) is a biologically heterogeneous disease accompanying various genetic and epigenetic alterations, and the molecular mechanisms underlying this disease are complex and not completely understood. Increasing evidence shows that abnormal microRNA (miRNA) expression is involved in GC tumorigenesis, but the role of specific miRNAs involved in this disease remains elusive. MiR-141 was previously reported to act as tumor suppressors or oncogenes in diverse cancers. However, their accurate expression, function and mechanism in GC are largely unclear. Here we found that the expression of miR-141 was significantly reduced in GC compared with paired adjacent normal tissues and was significantly correlated with a more aggressive phenotype of GC in patients. Ectopic expression of miR-141 mimics in GC cell lines resulted in reduced proliferation, invasion and migration, and inhibition of miR-141 in GC cell lines promoted cell proliferation, invasion and migration in vitro. We further demonstrated that miR-141 acted as tumor suppressors through targeting transcriptional co-activator with PDZ-binding motif (TAZ) in GC. Moreover, the inverse relationship between miR-141 and its target was verified in patients and xenograft mice. Finally, overexpression of miR-141 suppressed tumor growth and pulmonary metastasis in nude mice. Take together, we identified that miR-141 is a potent tumor suppressor in the stomach, and its growth inhibitory effects are, in part, mediated through its downstream target gene, TAZ. These findings implied that miR-141 might be employed as novel prognostic markers and therapeutic targets of GC.
authors: National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing 400038, PR China.
authors: Q-F
authors: QF
authors: Zuo
authors: Research and Service Center of Laboratory Medicine, ChengDu Military General Hospital, Chengdu 610083, PR China.
authors: R
authors: R
authors: Zhang
authors: National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing 400038, PR China.
authors: B-S
authors: BS
authors: Li
authors: General Surgery and Center of Minimally Invasive Gastrointestinal Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, PR China.
authors: Y-L
authors: YL
authors: Zhao
authors: National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing 400038, PR China.
authors: Y
authors: Y
authors: Zhuang
authors: National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing 400038, PR China.
authors: T
authors: T
authors: Yu
authors: National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing 400038, PR China.
authors: L
authors: L
authors: Gong
authors: National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing 400038, PR China.
authors: S
authors: S
authors: Li
authors: National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing 400038, PR China.
authors: B
authors: B
authors: Xiao
authors: National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing 400038, PR China.
authors: Q-M
authors: QM
authors: Zou
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001483:Base Sequence; D002465:Cell Movement; D049109:Cell Proliferation; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008175:Lung Neoplasms / Q000556:secondary*; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology*; D015534:Trans-Activators; D014157:Transcription Factors; D000091364:Transcriptional Coactivator with PDZ-Binding Motif Proteins; D023041:Xenograft Model Antitumor Assays
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C533895:MIRN141 microRNA, human; D035683:MicroRNAs; D015534:Trans-Activators; D014157:Transcription Factors; D000091364:Transcriptional Coactivator with PDZ-Binding Motif Proteins; C551991:WWTR1 protein, human
references: Crit Rev Oncol Hematol. 2009 Aug;71(2):127-64
references: 19230702
references: Oncogene. 2015 May 14;34(20):2556-65
references: 25043310
references: Br J Cancer. 2010 Jan 19;102(2):237-42
references: 19888225
references: Curr Biol. 2007 Dec 4;17(23):2054-60
references: 17980593
references: Mol Cell Biol. 2003 Feb;23(3):1004-13
references: 12529404
references: Am J Physiol Renal Physiol. 2012 Feb 1;302(3):F369-79
references: 22012804
references: PLoS One. 2014;9(2):e88393
references: 24551096
references: Proc Natl Acad Sci U S A. 2005 Dec 13;102(50):18034-9
references: 16332960
references: BMC Cancer. 2014;14:60
references: 24495377
references: Int J Mol Med. 2014 Apr;33(4):879-86
references: 24424572
references: Mol Cell Biochem. 2014 Mar;388(1-2):211-8
references: 24276755
references: Int J Oncol. 2014 Feb;44(2):459-66
references: 24285464
references: Lancet. 2005 Nov 19;366(9499):1784-93
references: 16298215
references: Nat Rev Genet. 2009 Oct;10(10):704-14
references: 19763153
references: Cancer Biol Ther. 2013 May;14(5):390-8
references: 23380592
references: Cancer Epidemiol Biomarkers Prev. 2010 Aug;19(8):1893-907
references: 20647400
references: Dev Cell. 2010 Oct 19;19(4):491-505
references: 20951342
references: Oncol Rep. 2012 Apr;27(4):1019-26
references: 22267008
references: J Biol Chem. 2009 May 15;284(20):13355-62
references: 19324877
references: Oncogene. 2011 May 5;30(18):2181-6
references: 21258416
references: Curr Opin Cell Biol. 2008 Dec;20(6):638-46
references: 18955139
references: Bioinformation. 2014 May 20;10(5):246-50
references: 24966529
references: Oncogene. 2013 Sep 5;32(36):4284-93
references: 23045278
references: Eur J Cancer. 2011 Apr;47(6):926-33
references: 21131195
references: J Surg Oncol. 2013 Mar;107(3):230-6
references: 23129495
references: Oncogene. 2010 Oct 28;29(43):5761-71
references: 20802530
references: Biochem J. 2005 May 15;388(Pt 1):217-25
references: 15628970
references: Genes Cancer. 2010 Nov;1(11):1115-8
references: 21779434
references: Genes Dev. 2011 Dec 15;25(24):2594-609
references: 22190458
references: Mol Cancer Res. 2011 Jul;9(7):824-33
references: 21628394
references: EMBO J. 2000 Dec 15;19(24):6778-91
references: 11118213
references: Nat Med. 2011 Dec;17(12):1627-35
references: 22101765
references: Nat Rev Cancer. 2006 Nov;6(11):857-66
references: 17060945
references: FEBS Lett. 2014 Aug 25;588(17):3055-61
references: 24945731
references: Carcinogenesis. 2012 Jun;33(6):1126-33
references: 22491715
references: Gut. 2013 Sep;62(9):1315-26
references: 22735571
references: Cell. 2011 Nov 11;147(4):759-72
references: 22078877
references: CA Cancer J Clin. 2011 Mar-Apr;61(2):69-90
references: 21296855
references: Clin Cancer Res. 2014 May 15;20(10):2617-30
references: 24647573
references: Cell Physiol Biochem. 2014;33(4):1003-12
references: 24732377
references: Science. 2005 Aug 12;309(5737):1074-8
references: 16099986
references: Cancer Res. 2008 Apr 15;68(8):2592-8
references: 18413727
references: Gut. 2015 Feb;64(2):203-14
references: 24870620
references: BMC Syst Biol. 2011;5:99
references: 21703006
references: J Gastroenterol. 2009;44(6):556-61
references: 19363643