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

33 Citations (Scopus)

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

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MicroRNAs
Ovarian Neoplasms
Up-Regulation
Cells
Neoplasm Metastasis
STAT3 Transcription Factor
RNA Polymerase II
Cell proliferation
Biomarkers
Transcription
Growth
Amplification
Transcription Factors
Chemical activation
Cell Proliferation
Apoptosis
Messenger RNA
Transcriptional Activation
Neoplasms
In Vitro Techniques

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Direct Upregulation of STAT3 by MicroRNA-551b-3p Deregulates Growth and Metastasis of Ovarian Cancer. / Chaluvally-Raghavan, Pradeep; Jeong, Kang Jin; Pradeep, Sunila; Silva, Andreia Machado; Yu, Shuangxing; Liu, Wenbin; Moss, Tyler; Rodriguez-Aguayo, Cristian; Zhang, Dong; Ram, Prahlad; Liu, Jinsong; Lu, Yiling; Lopez-Berestein, Gabriel; Calin, George A.; Sood, Anil K.; Mills, Gordon.

In: Cell Reports, Vol. 15, No. 7, 17.05.2016, p. 1493-1504.

Research output: Contribution to journalArticle

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, G 2016, 'Direct Upregulation of STAT3 by MicroRNA-551b-3p Deregulates Growth and Metastasis of Ovarian Cancer', Cell Reports, vol. 15, no. 7, pp. 1493-1504. https://doi.org/10.1016/j.celrep.2016.04.034
Chaluvally-Raghavan P, Jeong KJ, Pradeep S, Silva AM, Yu S, Liu W et al. Direct Upregulation of STAT3 by MicroRNA-551b-3p Deregulates Growth and Metastasis of Ovarian Cancer. Cell Reports. 2016 May 17;15(7):1493-1504. https://doi.org/10.1016/j.celrep.2016.04.034
Chaluvally-Raghavan, Pradeep ; Jeong, Kang Jin ; Pradeep, Sunila ; Silva, Andreia Machado ; Yu, Shuangxing ; Liu, Wenbin ; Moss, Tyler ; Rodriguez-Aguayo, Cristian ; Zhang, Dong ; Ram, Prahlad ; Liu, Jinsong ; Lu, Yiling ; Lopez-Berestein, Gabriel ; Calin, George A. ; Sood, Anil K. ; Mills, Gordon. / Direct Upregulation of STAT3 by MicroRNA-551b-3p Deregulates Growth and Metastasis of Ovarian Cancer. In: Cell Reports. 2016 ; Vol. 15, No. 7. pp. 1493-1504.
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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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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

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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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