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Series GSE31637

Query DataSets for GSE31637

Status

Public on Dec 31, 2011

Title

Tumor Suppressor BRCA1 epigenetically controls oncogenic miRNA-155

Organism

Mus musculus

Experiment type

Expression profiling by array
Non-coding RNA profiling by array

Summary

BRCA1, a well-known breast and ovarian cancer susceptibility gene with multiple interacting partners, is predicted to have diverse biological functions. However, to date its only well-established role is in the repair of damaged DNA and cell cycle regulation. In this regard, the etiopathological study of low penetrant variants of BRCA1 provides an opportunity to uncover its other physiologically important functions. Using this rationale, we studied the R1699Q variant of BRCA1, a potentially moderate risk variant, and found that it does not impair DNA damage repair but abrogates the repression of miR-155, a bona fide oncomir. We further show that in the absence of functional BRCA1, miR-155 is up-regulated in BRCA1-deficient mouse mammary epithelial cells, human and mouse BRCA1-deficienct breast tumor cell lines as well as tumors. Mechanistically, we found that BRCA1 represses miR-155 expression via its association with HDAC2, which deacetylates H2A and H3 on the miR-155 promoter. Finally, we show that over-expression of miR-155 accelerates whereas the knockdown of miR-155 attenuates the growth of tumor cell lines in vivo. Taken together, our findings demonstrate a new mode of tumor suppression by BRCA1 and reveal miR-155 as a potential therapeutic target for BRCA1-deficient tumors.

This SuperSeries is composed of the SubSeries listed below.

Overall design

Refer to individual Series.

Citation(s)

21946536

Submission date

Aug 24, 2011

Last update date

Feb 11, 2019

Contact name

Suhwan Chang

Organization name

National Cancer Institute