title: Anti-tumoral effects of miR-3189-3p in glioblastoma.
abstract: Glioblastoma is one of the most aggressive brain tumors. We have previously found up-regulation of growth differentiation factor 15 (GDF15) in glioblastoma cells treated with the anticancer agent fenofibrate. Sequence analysis of GDF15 revealed the presence of a microRNA, miR-3189, in the single intron. We then asked whether miR-3189 was expressed in clinical samples and whether it was functional in glioblastoma cells. We found that expression of miR-3189-3p was down-regulated in astrocytoma and glioblastoma clinical samples compared with control brain tissue. In vitro, the functionality of miR-3189-3p was tested by RNA-binding protein immunoprecipitation, and miR-3189-3p coimmunoprecipitated with Argonaute 2 together with two of its major predicted gene targets, the SF3B2 splicing factor and the guanine nucleotide exchange factor p63RhoGEF. Overexpression of miR-3189-3p resulted in a significant inhibition of cell proliferation and migration through direct targeting of SF3B2 and p63RhoGEF, respectively. Interestingly, miR-3189-3p levels were increased by treatment of glioblastoma cells with fenofibrate, a lipid-lowering drug with multiple anticancer activities. The attenuated expression of miR-3189-3p in clinical samples paralleled the elevated expression of SF3B2, which could contribute to the activation of SF3B2 growth-promoting pathways in these tumors. Finally, miR-3189-3p-mediated inhibition of tumor growth in vivo further supported the function of this microRNA as a tumor suppressor.
authors: From the Department of Medicine and the Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112.
authors: Duane
authors: D
authors: Jeansonne
authors: From the Department of Medicine and the Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112.
authors: Mariacristina
authors: M
authors: DeLuca
authors: From the Department of Medicine and.
authors: Luis
authors: L
authors: Marrero
authors: From the Department of Medicine and the Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112.
authors: Adam
authors: A
authors: Lassak
authors: From the Department of Medicine and the Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112.
authors: Marco
authors: M
authors: Pacifici
authors: From the Department of Medicine and the Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112.
authors: Dorota
authors: D
authors: Wyczechowska
authors: From the Department of Medicine and the Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112.
authors: Anna
authors: A
authors: Wilk
authors: From the Department of Medicine and the Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112.
authors: Krzysztof
authors: K
authors: Reiss
authors: From the Department of Medicine and the Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112 fperuz@lsuhsc.edu.
authors: Francesca
authors: F
authors: Peruzzi
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D055436:Growth Differentiation Factor 15 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D009368:Neoplasm Transplantation; D034622:RNA Interference; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D064067:Rho Guanine Nucleotide Exchange Factors / Q000096:biosynthesis / Q000235:genetics
chemical_list: C475063:ARHGEF25 protein, human; C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15; C000598218:MIRN3189 microRNA, human; D035683:MicroRNAs; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins; D064067:Rho Guanine Nucleotide Exchange Factors; C486348:SF3B2 protein, human
keywords: Cell Migration; Cell Proliferation; Glioblastoma; MicroRNA (miRNA); Tumor Suppressor Gene
references: Cell Cycle. 2003 Jul-Aug;2(4):333-8
references: 12851485
references: Mol Syst Biol. 2012;8:573
references: 22415777
references: J Cell Physiol. 2010 Sep;224(3):626-35
references: 20578239
references: Mol Cell Biol. 2015 Jan;35(1):182-98
references: 25332241
references: Genes Chromosomes Cancer. 2013 Nov;52(11):1042-52
references: 23913824
references: Cell. 2007 Jul 13;130(1):89-100
references: 17599402
references: J Cell Physiol. 2013 May;228(5):1070-5
references: 23042033
references: Neurosurg Clin N Am. 2012 Apr;23(2):307-22, ix
references: 22440874
references: Int J Cancer. 2008 Sep 1;123(5):1015-24
references: 18546270
references: Cell Cycle. 2012 Jul 15;11(14):2660-71
references: 22732497
references: J Biochem Mol Biol. 2006 Nov 30;39(6):649-55
references: 17129398
references: Cancer Res. 2009 Mar 1;69(5):2091-9
references: 19244127
references: Biochem Pharmacol. 2013 Mar 1;85(5):597-606
references: 23220538
references: Biochem Biophys Res Commun. 2013 Jan 25;430(4):1277-82
references: 23261467
references: Mediators Inflamm. 2013;2013:641851
references: 23737651
references: Mol Cell Biol. 1995 Aug;15(8):4215-24
references: 7623816
references: Genes (Basel). 2013 Mar 04;4(1):46-64
references: 24705102
references: Mol Cancer. 2010;9:159
references: 20569465
references: Proc Natl Acad Sci U S A. 2013 Jul 9;110(28):11499-504
references: 23798430
references: PLoS One. 2010;5(3):e9685
references: 20300190
references: Cancer Res. 2013 Oct 15;73(20):6206-18
references: 24008316
references: N Engl J Med. 2005 Mar 10;352(10):997-1003
references: 15758010
references: Cell Mol Life Sci. 2007 Feb;64(4):458-78
references: 17260089
references: Proc Natl Acad Sci U S A. 2008 Jan 22;105(3):985-90
references: 18199835
references: Curr Biol. 2003 Dec 2;13(23):R925-36
references: 14654021
references: J Cell Physiol. 2008 Sep;216(3):764-70
references: 18381601
references: Angiogenesis. 2009;12(3):221-9
references: 19357976
references: FEBS Lett. 2013 Mar 18;587(6):698-705
references: 23380069
references: J Biol Chem. 2008 Nov 28;283(48):33129-37
references: 18801729
references: FASEB J. 2010 Jul;24(7):2292-300
references: 20181935
references: Mol Cell. 2008 Oct 10;32(1):43-56
references: 18851832
references: Neoplasia. 2014 Oct;16(10):874-82
references: 25379024
references: BMC Cancer. 2011;11:146
references: 21504622