Let-7 repression leads to HMGA2 overexpression in uterine leiomyosarcoma.
Overexpression of HMGA2 is common in uterine leiomyomas (ULM). The expression of HMGA2 in its malignant counterpart - uterine leiomyosarcomas (ULMS) remains undetermined. Recently it has been shown that repression of HMGA2 by microRNA let-7s is a critical molecular regulatory mechanism associated with tumour growth in many tumours and cell types, including leiomyomas. To test whether HMGA2 and let-7s play a role in ULMS, we examined the levels of endogenous HMGA2 and let-7 expression and found a significant correlation between these two molecules in a case-matched cohort of human ULMS. We found that overexpression of HMGA2 and let-7-mediated HMGA2 repression is a relevant molecular alteration in ULMS. Disrupting the control of HMGA2 and let-7 pairs promotes ULMS cell growth in vitro.
Shi
Guizhi
G
Department of Pathology, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611, USA.
Perle
Mary Ann
MA
Mittal
Khush
K
Chen
Hua
H
Zou
Xuanyi
X
Narita
Masashi
M
Hernando
Eva
E
Lee
Peng
P
Wei
Jian-Jun
JJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D049109:Cell Proliferation; D015331:Cohort Studies; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D025743:HMGA2 Protein / Q000096:biosynthesis*; D006801:Humans; D017403:In Situ Hybridization; D007890:Leiomyosarcoma / Q000378:metabolism*; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D008875:Middle Aged; D014594:Uterine Neoplasms / Q000378:metabolism*
D025743:HMGA2 Protein; D035683:MicroRNAs; C487931:mirnlet7 microRNA, human