Estrogen receptor-α regulation of microRNA-590 targets FAM171A1-a modifier of breast cancer invasiveness

Oncogenesis  2019 Jan; 8(1): 5. | https://dx.doi.org/10.1038%2Fs41389-018-0113-z  

Rahul Sanawar, Vipin Mohan Dan, Thankayyan R. Santhoshkumar, Rakesh Kumar & M. Radhakrishna Pillai

The pathobiology and aggressiveness of the triple negative breast cancer (TNBC) are influenced by genes that are preferentially expressed in TNBC cells. However, the nature of such genes with the role in invasiveness of TNBC cells is not fully understood. Here, we identified FAM171A1, member (A1) of the family with sequence similarity 171, as an overexpressed candidate gene in TNBC cells and tumors as compared to estrogen receptor-alpha (ERα) positive breast cancer. We found that the expression of FAM171A1 correlates well with the loss of ERα as well as its newly identified target miR590-5p in TNBC but not in ERα-positive cells. In addition, we report that ERα regulates FAM171A1expression through a mechanism which involves ERα stimulation of miR590-5p expression via binding to its promoter, and in-turn, miR590-5p suppression of FAM171A1 expression. Further, we found that the levels of FAM171A1 correlate well with cancer cell aggressiveness as depletion or overexpression of FAM171A1 confers reduced or increased ability of TNBC cells to form mammospheres, respectively in accordance with the previous report of increased mammosphere formation potential of metastatic cells. In brief, results presented here have demonstrated that ERα regulation of FAM171A1 expression via miR590-5p explains the molecular basis of the noticed reduced levels of FAM171A1 in ER-positive breast cancer cells and that FAM171A1 is a preferably TNBC- overexpressed gene. Further, the noted loss of ERα–miR590-5p axis may upregulate the expression of FAM171A1 and consequently, resulting aggressiveness of TNBC cells. These findings suggest that FAM171A1 might represent a potentially novel therapeutic target for TNBC tumors.

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