Estrogen receptor ? signaling regulates breast tumor-initiating cells by down-regulating miR-140 which targets the transcription factor SOX2.

ABSTRACT: Several reports have indicated that miR-140, a possible tumor suppressor microRNA (miR), is down-regulated in breast tumors compared with normal breast tissues. However, the role of miR-140 in breast tumorigenesis is unclear. We initiated studies that examined estrogen receptor ? (ER?) signaling in the tissue-specific regulation of miR-140 in breast cancer. We found that estrogen stimulation of ER?-positive breast cancer cells resulted in decreased miR-140 expression. We performed promoter analyses and examined predicted ER? binding elements in the miR-140 promoter using luciferase constructs of a miR-140 promoter deletion series. Our studies revealed that ER? binds to one specific estrogen response element flanking the miR-140 promoter and consequently suppresses miR-140 transcription. We found that the stem cell self-renewal regulator SOX2 is a novel target of miR-140, and that this miR-140/SOX2 pathway critically regulates breast tumor-initiating cell survival, providing a new link between ER? signaling and breast cancer stem cell maintenance.

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC3510847 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature