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

Pradeep Chaluvally-Raghavan, Kang Jin Jeong, Sunila Pradeep, Andreia Machado Silva, Shuangxing Yu, Wenbin Liu, Tyler Moss, Cristian Rodriguez-Aguayo, Dong Zhang, Prahlad Ram, Jinsong Liu, Yiling Lu, Gabriel Lopez-Berestein, George A. Calin, Anil K. Sood, Gordon Mills

Research output: Contribution to journalArticle

41 Scopus 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.

Original languageEnglish (US)
Pages (from-to)1493-1504
Number of pages12
JournalCell Reports
Volume15
Issue number7
DOIs
StatePublished - May 17 2016
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Chaluvally-Raghavan, P., Jeong, K. J., Pradeep, S., Silva, A. M., Yu, S., Liu, W., Moss, T., Rodriguez-Aguayo, C., Zhang, D., Ram, P., Liu, J., Lu, Y., Lopez-Berestein, G., Calin, G. A., Sood, A. K., & Mills, G. (2016). Direct Upregulation of STAT3 by MicroRNA-551b-3p Deregulates Growth and Metastasis of Ovarian Cancer. Cell Reports, 15(7), 1493-1504. https://doi.org/10.1016/j.celrep.2016.04.034