Estrogen receptor-regulated microRNAs contribute to the BCL2/BAX imbalance in endometrial adenocarcinoma and precancerous lesions.
Uncontrolled estrogen exposure can induce an imbalance in BCL2/BAX expression in endometrial cells, leading to precancerous lesions and type I endometrial adenocarcinoma. This study aimed to explore the mechanism underlying this phenomenon. We show that the activated estrogen receptor can suppress the expression of BAX by upregulating a group of microRNAs including hsa-let-7 family members and hsa-miR-27a, thereby promoting an increased BCL2/BAX ratio as well as enhanced survival and proliferation in the affected cells. These ER-regulated hsa-let-7 microRNAs can be detected in most hyperplastic endometria, suggesting their potential utility as indicators of estrogen over-exposure.
Department of Obstetrics and Gynecology, Fengxian Central Hospital, Shanghai 201400, PR China. rongzhang@163.com
Rong
R
Zhang
Yifeng
Y
He
Xueli
X
Zhang
Baolin
B
Xing
Youhua
Y
Sheng
Huan
H
Lu
Zhenhong
Z
Wei
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology*; D000328:Adult; D045744:Cell Line, Tumor; D016889:Endometrial Neoplasms / Q000235:genetics / Q000473:pathology*; D005260:Female; D019254:Genes, bcl-2; D006801:Humans; D035683:MicroRNAs / Q000502:physiology*; D008875:Middle Aged; D011230:Precancerous Conditions / Q000235:genetics / Q000473:pathology*; D011401:Promoter Regions, Genetic; D011960:Receptors, Estrogen / Q000502:physiology*; D051028:bcl-2-Associated X Protein / Q000235:genetics*
C494826:BAX protein, human; D035683:MicroRNAs; D011960:Receptors, Estrogen; D051028:bcl-2-Associated X Protein; C487931:mirnlet7 microRNA, human