TY - JOUR
T1 - Direct Upregulation of STAT3 by MicroRNA-551b-3p Deregulates Growth and Metastasis of Ovarian Cancer
AU - Chaluvally-Raghavan, Pradeep
AU - Jeong, Kang Jin
AU - Pradeep, Sunila
AU - Silva, Andreia Machado
AU - Yu, Shuangxing
AU - Liu, Wenbin
AU - Moss, Tyler
AU - Rodriguez-Aguayo, Cristian
AU - Zhang, Dong
AU - Ram, Prahlad
AU - Liu, Jinsong
AU - Lu, Yiling
AU - Lopez-Berestein, Gabriel
AU - Calin, George A.
AU - Sood, Anil K.
AU - Mills, Gordon B.
N1 - Funding Information:
G.B.M. is supported by NCI (2P50CA083639-11, 5P50CA058183-17, and 5R01CA123219-01), Stand up to Cancer/American Association of Cancer Research (SU2C-AACR-DT0209), Adelson Medical Research Foundation, and Komen Promise Grant (KG081694). P.C.-R. is supported by Ovarian Cancer Research Fund and Marsha Rivkin Center for Ovarian Cancer Research. A.K.S. is supported by NCI (P50CA083639, P50CA098258, U54CA151668, and UH2 TR000943). G.A.C. is supported in part by the NIH/NCI grants 1UH2TR00943-01 and 1 R01 CA182905-01.
Publisher Copyright:
© 2016 The Authors.
PY - 2016/5/17
Y1 - 2016/5/17
N2 - 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.
AB - 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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U2 - 10.1016/j.celrep.2016.04.034
DO - 10.1016/j.celrep.2016.04.034
M3 - Article
C2 - 27160903
AN - SCOPUS:84964941322
SN - 2211-1247
VL - 15
SP - 1493
EP - 1504
JO - Cell Reports
JF - Cell Reports
IS - 7
ER -