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 - 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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UR - http://www.scopus.com/inward/citedby.url?scp=84964941322&partnerID=8YFLogxK
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 -