HMGA2-mediated tumorigenesis through angiogenesis in leiomyoma.
Animals
Carcinogenesis
/ metabolism
Female
HEK293 Cells
HMGA2 Protein
/ biosynthesis
Human Umbilical Vein Endothelial Cells
/ metabolism
Humans
Leiomyoma
/ metabolism
Mice
Mice, Inbred NOD
Mice, SCID
Neovascularization, Pathologic
/ metabolism
Uterine Neoplasms
/ metabolism
Xenograft Model Antitumor Assays
/ methods
AKT pathway
HMGA2
Leiomyoma
angiogenesis
xenograft
Journal
Fertility and sterility
ISSN: 1556-5653
Titre abrégé: Fertil Steril
Pays: United States
ID NLM: 0372772
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
20
03
2020
revised:
25
05
2020
accepted:
28
05
2020
pubmed:
2
9
2020
medline:
19
5
2021
entrez:
2
9
2020
Statut:
ppublish
Résumé
To study the role of HMGA2 in promoting angiogenesis in uterine leiomyoma (LM). This study involved evaluation of vessel density and angiogenic factors in leiomyomas with HMGA2 overexpression; examining angiogenic factor expression and AKT signaling in myometrial (MM) and leiomyoma cells by introducing HMGA2 overexpression in vitro; and exploring vessel formation induced by HMGA2 overexpression both in vitro and in vivo. University research laboratory. None. None. The main outcome measures include vessel density in leiomyomas with HMGA2 (HMGA2-LM) or MED12 (MED12-LM) alteration; angiogenic factor expression in primary leiomyoma and in vitro cell line model; and vessel formation in leiomyoma cells with HMGA2 overexpression in vitro and in vivo. Angiogenic factors and receptors were significantly upregulated at mRNA and protein levels in HMGA2-LM. Specifically, HMGA2-LM exhibited increased expression of VEGFA, EGF, bFGF, TGFα, VEGFR1, and VEGFR2 compared to MED12-LM and myometrium. Overexpression of HMGA2 in MM and LM cell lines resulted in increased secretion of angiogenesis-associated factors. Secreted factors promoted human umbilical vein endothelial cell (HUVEC) migration, tube formation, and wound healing. HMGA2 overexpression upregulated IGF2BP2 and pAKT, and silencing the IGF2BP2 gene reduced pAKT levels and reduced HUVEC migration. Myometrial cells with stable HMGA2 overexpression exhibited increased colony formation and cell growth in vitro and formed xenografts with increased blood vessels. HMGA2-LM have a high vasculature density, which likely contributes to tumor growth and disease burden of this leiomyoma subtype. HMGA2 plays an important role in angiogenesis and the involvement of IGF2BP2-mediated pAKT activity in angiogenesis, which provides a potential novel target for therapy for this subtype of LM.
Identifiants
pubmed: 32868105
pii: S0015-0282(20)30527-6
doi: 10.1016/j.fertnstert.2020.05.036
pmc: PMC7655683
mid: NIHMS1599719
pii:
doi:
Substances chimiques
HMGA2 Protein
0
HMGA2 protein, human
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1085-1096Subventions
Organisme : NICHD NIH HHS
ID : P01 HD057877
Pays : United States
Organisme : NICHD NIH HHS
ID : P50 HD098580
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2020 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
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