Let-7 prevents early cancer progression by suppressing expression of the embryonic gene HMGA2.
The microRNA let-7 regulates late embryonic development by suppressing expression of a number of genes such as c-myc and RAS as well as the embryonic gene high mobility group, A2 (HMGA2). We now demonstrate that HMGA2 is more efficiently targeted by let-7 than RAS. Its expression inversely correlates with the expression of let-7 in the NCI60 cells lines, and the expression of RAS does not change when amounts of let-7 that efficiently silence expression of HMGA2 are introduced into tumor cells. We did not find a difference in the expression of HMGA2 between primary ovarian cancer samples and matching metastases, suggesting that the expression of HMGA2 represents an early event during cancer progression. The late repression of HMGA2 by let-7 during embryonic development, and the early reexpression of HMGA2 during cancer development, is in line with the hypothesis that cancer development represents a case of reverse embryogenesis.
Park
Sun-Mi
SM
The Ben May Department for Cancer Research, University of Chicago, Chicago, Illinois 60637, USA.
Shell
Scott
S
Radjabi
Amir Reza
AR
Schickel
Robert
R
Feig
Christine
C
Boyerinas
Ben
B
Dinulescu
Daniela M
DM
Lengyel
Ernst
E
Peter
Marcus E
ME
D045744:Cell Line, Tumor; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D025743:HMGA2 Protein / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D035683:MicroRNAs / Q000502:physiology*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000517:prevention & control*; D013489:Suppression, Genetic
D025743:HMGA2 Protein; D035683:MicroRNAs; C487931:mirnlet7 microRNA, human