Increased expression of angiogenic genes in the brains of mouse meg3-null embryos.
Maternally expressed gene 3 (MEG3) is a noncoding RNA highly expressed in the normal human brain and pituitary. Expression of MEG3 is lost in gonadotroph-derived clinically nonfunctioning pituitary adenomas. Meg3 knockout mice were generated to identify targets and potential functions of this gene in embryonic development and tumorigenesis. Gene expression profiles were compared in the brains of Meg3-null embryos and wild-type littermate controls using microarray analysis. Microarray data were analyzed with GeneSifter, which uses Kyoto Encyclopedia of Genes and Genomes pathways and Gene Ontology classifications to identify signaling cascades and functional categories of interest within the dataset. Differences were found in signaling pathways and ontologies related to angiogenesis between wild-type and knockout embryos. Quantitative RT-PCR and immunohistological staining showed increased expression of some Vascular Endothelial Growth Factor pathway genes and increased cortical microvessel density in the Meg3-null embryos. In conclusion, Meg3 may play an important role in control of vascularization in the brain and may function as a tumor suppressor in part by inhibiting angiogenesis.
Gordon
Francesca E
FE
Neuroendocrine Unit, Bulfinch 457B, Massachusetts General Hospital, 55 Fruit Street, Boston, Massachusetts 02114, USA.
Nutt
Catherine L
CL
Cheunsuchon
Pornsuk
P
Nakayama
Yuki
Y
Provencher
Katelyn A
KA
Rice
Kimberley A
KA
Zhou
Yunli
Y
Zhang
Xun
X
Klibanski
Anne
A
D000818:Animals; D001921:Brain / Q000196:embryology* / Q000378:metabolism*; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic / Q000235:genetics / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D062085:RNA, Long Noncoding; D020133:Reverse Transcriptase Polymerase Chain Reaction; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism
C422882:MEG3 non-coding RNA, mouse; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011506:Proteins; D062085:RNA, Long Noncoding; D040301:Vascular Endothelial Growth Factor Receptor-2
Dev Dyn. 1998 Jun;212(2):214-28
9626496
Oncogene. 2004 Jan 15;23(2):434-45
14724572
J Cell Biol. 2003 Jun 23;161(6):1163-77
12810700
J Biol Chem. 2004 Sep 10;279(37):39175-85
15247219
Clin Cancer Res. 2009 Jan 15;15(2):492-501
19147754
Clin Lymphoma Myeloma. 2008 Jun;8(3):171-5
18650181
Nucleic Acids Res. 2007;35(14):4583-96
17586813
Biochim Biophys Acta. 2008 Mar;1778(3):794-809
17961505
Dev Biol. 2007 Jun 15;306(2):810-23
17449025
Nature. 2008 Jul 31;454(7204):656-60
18594512
Development. 2008 Sep;135(18):3113-24
18725516
Proc Natl Acad Sci U S A. 2002 Jan 8;99(1):383-8
11756651
Dev Biol. 2009 Jan 1;325(1):151-61
18996108
Mol Endocrinol. 2001 Mar;15(3):429-40
11222744
Circ Res. 2007 Jan 5;100(1):61-9
17138942
J Clin Endocrinol Metab. 2002 Sep;87(9):4238-44
12213878
Cell Death Differ. 2010 Mar;17(3):499-512
19834490
Br J Cancer. 2005 Apr 25;92(8):1574-80
15798773
Nat Genet. 2000 May;25(1):25-9
10802651
Development. 2008 Aug;135(15):2531-41
18579678
Nat Rev Cancer. 2002 Nov;2(11):836-49
12415254
EMBO J. 2000 Aug 1;19(15):4064-73
10921887
Am J Pathol. 1997 Sep;151(3):671-7
9284815
J Biol Chem. 2007 Aug 24;282(34):24731-42
17569660
Hum Pathol. 2005 Oct;36(10):1090-5
16226108
Eur J Endocrinol. 2008 Mar;158(3):287-94
18299460
Endocr Relat Cancer. 2008 Dec;15(4):905-15
18780796
Pituitary. 2007;10(1):61-5
17318437
Endocrinology. 2002 Dec;143(12):4837-45
12446611
Mol Cancer Ther. 2008 Apr;7(4):880-9
18413801
Cancer Res. 2003 Apr 1;63(7):1602-7
12670911
Development. 2007 May;134(10):1833-43
17428830
J Biol Chem. 2000 Apr 7;275(14):10661-72
10744763
Nat Med. 2003 Jun;9(6):669-76
12778165
Cancer Res. 2001 Sep 15;61(18):6952-7
11559575
Gene Expr Patterns. 2006 Apr;6(4):394-9
16356785
Dev Cell. 2009 Jan;16(1):70-82
19154719
J Clin Endocrinol Metab. 2003 Nov;88(11):5119-26
14602737
J Clin Endocrinol Metab. 2008 Oct;93(10):4119-25
18628527
J Clin Endocrinol Metab. 2005 Apr;90(4):2179-86
15644399
Endocr Rev. 2003 Oct;24(5):600-32
14570746
J Cell Biol. 2008 Jun 2;181(5):847-58
18504303
Nucleic Acids Res. 2000 Jan 1;28(1):27-30
10592173
Dev Cell. 2009 Feb;16(2):196-208
19217422
Blood. 2006 Feb 1;107(3):931-9
16219802
J Biol Chem. 2003 Oct 17;278(42):41237-45
12900413
Proc Natl Acad Sci U S A. 1991 Oct 15;88(20):9026-30
1717995
Science. 1992 Feb 21;255(5047):989-91
1312256
Genes Cells. 2000 Mar;5(3):211-20
10759892
Nature. 2007 Feb 15;445(7129):776-80
17259973
Development. 2004 Nov;131(22):5539-50
15496443
J Biol Chem. 1994 Oct 28;269(43):26988-95
7929439
Nature. 1995 Jul 6;376(6535):66-70
7596436
J Biol Chem. 2007 Jan 5;282(1):426-35
17085436
Arterioscler Thromb Vasc Biol. 2006 Sep;26(9):1991-7
16763158
Eur J Endocrinol. 2007 Feb;156(2):217-24
17287411