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  • miRNA551b-3p Activates an Oncostatin Signaling Module for the Progression of Triple-Negative Breast Cancer.

miRNA551b-3p Activates an Oncostatin Signaling Module for the Progression of Triple-Negative Breast Cancer.

Cell reports (2019-12-26)
Deepak Parashar, Anjali Geethadevi, Miriam Ragle Aure, Jyotsna Mishra, Jasmine George, Changliang Chen, Manoj K Mishra, Andliena Tahiri, Wei Zhao, Bindu Nair, Yiling Lu, Lingegowda S Mangala, Cristian Rodriguez-Aguayo, Gabriel Lopez-Berestein, Amadou K S Camara, Mingyu Liang, Janet S Rader, Ramani Ramchandran, Ming You, Anil K Sood, Vessela N Kristensen, Gordon B Mills, Sunila Pradeep, Pradeep Chaluvally-Raghavan
ABSTRACT

Genomic amplification of 3q26.2 locus leads to the increased expression of microRNA 551b-3p (miR551b-3p) in triple-negative breast cancer (TNBC). Our results demonstrate that miR551b-3p translocates to the nucleus with the aid of importin-8 (IPO8) and activates STAT3 transcription. As a consequence, miR551b upregulates the expression of oncostatin M receptor (OSMR) and interleukin-31 receptor-α (IL-31RA) as well as their ligands OSM and IL-31 through STAT3 transcription. We defined this set of genes induced by miR551b-3p as the "oncostatin signaling module," which provides oncogenic addictions in cancer cells. Notably, OSM is highly expressed in TNBC, and the elevated expression of OSM associates with poor outcome in estrogen-receptor-negative breast cancer patients. Conversely, targeting miR551b with anti-miR551b-3p reduced the expression of the OSM signaling module and reduced tumor growth, as well as migration and invasion of breast cancer cells.

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