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.
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