Faculty Collaboration Database

miRNA551b-3p Activates an Oncostatin Signaling Module for the Progression of Triple-Negative Breast Cancer. Cell Rep 2019 Dec 24;29(13):4389-4406.e10

Date

12/26/2019

Pubmed ID

31875548

Pubmed Central ID

PMC7380555

DOI

10.1016/j.celrep.2019.11.085

Scopus ID

2-s2.0-85076674271 (requires institutional sign-in at Scopus site)   62 Citations

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.

Author List

Parashar D, Geethadevi A, Aure MR, Mishra J, George J, Chen C, Mishra MK, Tahiri A, Zhao W, Nair B, Lu Y, Mangala LS, Rodriguez-Aguayo C, Lopez-Berestein G, Camara AKS, Liang M, Rader JS, Ramchandran R, You M, Sood AK, Kristensen VN, Mills GB, Pradeep S, Chaluvally-Raghavan P

Authors

Amadou K. Camara PhD Professor in the Anesthesiology department at Medical College of Wisconsin
Pradeep Chaluvally-Raghavan PhD Associate Professor in the Obstetrics and Gynecology department at Medical College of Wisconsin
Anjali Geethadevi PHD Research Scientist I in the Obstetrics and Gynecology department at Medical College of Wisconsin
Deepak Parashar PhD Assistant Professor in the Medicine department at Medical College of Wisconsin
Sunila Pradeep PhD Associate Professor in the Obstetrics and Gynecology department at Medical College of Wisconsin
Janet Sue Rader MD Chair, Professor in the Obstetrics and Gynecology department at Medical College of Wisconsin
Ramani Ramchandran PhD Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Carcinogenesis
Cell Line, Tumor
Cell Movement
Cell Nucleus
Cell Proliferation
Disease Progression
Gene Expression Regulation, Neoplastic
Gene Regulatory Networks
Humans
Mice, Nude
MicroRNAs
Molecular Targeted Therapy
Neoplasm Invasiveness
Oncostatin M
STAT3 Transcription Factor
Signal Transduction
Transcription, Genetic
Transcriptional Activation
Triple Negative Breast Neoplasms
Up-Regulation
beta Karyopherins