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Direct Upregulation of STAT3 by MicroRNA-551b-3p Deregulates Growth and Metastasis of Ovarian Cancer.

P. Chaluvally-Raghavan,K. Jeong,S. Pradeep,Andreia M. Silva,Shuangxing Yu,Wenbin Liu,T. Moss,Cristian Rodríguez-Aguayo,Dong Zhang,Prahlad T. Ram,Jinsong Liu,Yiling Lu,G. Lopez-Berestein,G. Calin,A. Sood,G. Mills

Published 2016 in Cell Reports

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.

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