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Direct Upregulation of STAT3 by MicroRNA-551b-3p Deregulates Growth and Metastasis of Ovarian Cancer. Cell Rep 2016 05 17;15(7):1493-1504

Date

05/11/2016

Pubmed ID

27160903

Pubmed Central ID

PMC4914391

DOI

10.1016/j.celrep.2016.04.034

Scopus ID

2-s2.0-84964941322   48 Citations

Abstract

3q26.2 amplification in high-grade serous ovarian cancer leads to increased expression of mature microRNA miR551b-3p, which is associated with poor clinical outcome. Importantly, miR551b-3p contributes to resistance to apoptosis and increased survival and proliferation of cancer cells in vitro and in vivo. miR551b-3p upregulates STAT3 protein levels, and STAT3 is required for the effects of miR551b-3p on cell proliferation. Rather than decreasing levels of target mRNA as expected, we demonstrate that miR551b-3p binds a complementary sequence on the STAT3 promoter, recruiting RNA polymerase II and the TWIST1 transcription factor to activate STAT3 transcription, and thus directly upregulates STAT3 expression. Furthermore, anti-miR551b reduced STAT3 expression in ovarian cancer cells in vitro and in vivo and reduced ovarian cancer growth in vivo. Together, our data demonstrate a role for miR551b-3p in transcriptional activation. Thus, miR551b-3p represents a promising candidate biomarker and therapeutic target in ovarian cancer.

Author List

Chaluvally-Raghavan P, Jeong KJ, Pradeep S, Silva AM, Yu S, Liu W, Moss T, Rodriguez-Aguayo C, Zhang D, Ram P, Liu J, Lu Y, Lopez-Berestein G, Calin GA, Sood AK, Mills GB

Authors

Pradeep Chaluvally-Raghavan PhD Associate Professor in the Obstetrics and Gynecology department at Medical College of Wisconsin
Sunila Pradeep PhD Assistant Professor in the Obstetrics and Gynecology department at Medical College of Wisconsin




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

Animals
Cell Line, Tumor
Cell Proliferation
Cell Self Renewal
Cell Survival
Down-Regulation
Female
Gene Amplification
Gene Expression Regulation, Neoplastic
Gene Knockdown Techniques
Gene Silencing
Humans
Mice, Nude
MicroRNAs
Neoplasm Metastasis
Neoplasms, Glandular and Epithelial
Nuclear Proteins
Ovarian Neoplasms
Promoter Regions, Genetic
RNA Polymerase II
STAT3 Transcription Factor
Spheroids, Cellular
Transcription, Genetic
Treatment Outcome
Tumor Burden
Twist-Related Protein 1
Up-Regulation