Super-Enhancer-Associated LncRNA UCA1 Interacts Directly with AMOT to Activate YAP Target Genes in Epithelial Ovarian Cancer

Xianzhi Lin; Tassja J. Spindler; Marcos Abraão de Souza Fonseca; Rosario I. Corona; Ji Heui Seo; Felipe Segato Dezem; L. Li; Janet M. Lee; Henry W. Long; Thomas A. Sellers; Beth Y. Karlan; Houtan Noushmehr; Matthew L. Freedman; Simon A. Gayther; Kate Lawrenson

doi:10.1016/j.isci.2019.06.025

Super-Enhancer-Associated LncRNA UCA1 Interacts Directly with AMOT to Activate YAP Target Genes in Epithelial Ovarian Cancer

Xianzhi Lin, Tassja J. Spindler, Marcos Abraão de Souza Fonseca, Rosario I. Corona, Ji Heui Seo, Felipe Segato Dezem, L. Li, Janet M. Lee, Henry W. Long, Thomas A. Sellers, Beth Y. Karlan, Houtan Noushmehr, Matthew L. Freedman, Simon A. Gayther, Kate Lawrenson

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62 Scopus citations

Abstract

Long noncoding RNAs (lncRNAs) have emerged as critical regulators of tumorigenesis, and yet their mechanistic roles remain challenging to characterize. Here, we integrate functional proteomics with lncRNA-interactome profiling to characterize Urothelial Cancer Associated 1 (UCA1), a candidate driver of ovarian cancer development. Reverse phase protein array (RPPA) analysis indicates that UCA1 activates transcription coactivator YAP and its target genes. In vivo RNA antisense purification (iRAP) of UCA1 interacting proteins identified angiomotin (AMOT), a known YAP regulator, as a direct binding partner. Loss-of-function experiments show that AMOT mediates YAP activation by UCA1, as UCA1 enhances the AMOT-YAP interaction to promote YAP dephosphorylation and nuclear translocation. Together, we characterize UCA1 as a lncRNA regulator of Hippo-YAP signaling and highlight the UCA1-AMOT-YAP signaling axis in ovarian cancer development.

Original language	English (US)
Pages (from-to)	242-255
Number of pages	14
Journal	iScience
Volume	17
DOIs	https://doi.org/10.1016/j.isci.2019.06.025
State	Published - Jul 26 2019
Externally published	Yes

Keywords

Cancer Systems Biology
Omics
Proteomics
Systems Biology

ASJC Scopus subject areas

General

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10.1016/j.isci.2019.06.025

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Lin, X., Spindler, T. J., de Souza Fonseca, M. A., Corona, R. I., Seo, J. H., Dezem, F. S., Li, L., Lee, J. M., Long, H. W., Sellers, T. A., Karlan, B. Y., Noushmehr, H., Freedman, M. L., Gayther, S. A., & Lawrenson, K. (2019). Super-Enhancer-Associated LncRNA UCA1 Interacts Directly with AMOT to Activate YAP Target Genes in Epithelial Ovarian Cancer. iScience, 17, 242-255. https://doi.org/10.1016/j.isci.2019.06.025

Lin, X, Spindler, TJ, de Souza Fonseca, MA, Corona, RI, Seo, JH, Dezem, FS, Li, L, Lee, JM, Long, HW, Sellers, TA, Karlan, BY, Noushmehr, H, Freedman, ML, Gayther, SA & Lawrenson, K 2019, 'Super-Enhancer-Associated LncRNA UCA1 Interacts Directly with AMOT to Activate YAP Target Genes in Epithelial Ovarian Cancer', iScience, vol. 17, pp. 242-255. https://doi.org/10.1016/j.isci.2019.06.025

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title = "Super-Enhancer-Associated LncRNA UCA1 Interacts Directly with AMOT to Activate YAP Target Genes in Epithelial Ovarian Cancer",

abstract = "Long noncoding RNAs (lncRNAs) have emerged as critical regulators of tumorigenesis, and yet their mechanistic roles remain challenging to characterize. Here, we integrate functional proteomics with lncRNA-interactome profiling to characterize Urothelial Cancer Associated 1 (UCA1), a candidate driver of ovarian cancer development. Reverse phase protein array (RPPA) analysis indicates that UCA1 activates transcription coactivator YAP and its target genes. In vivo RNA antisense purification (iRAP) of UCA1 interacting proteins identified angiomotin (AMOT), a known YAP regulator, as a direct binding partner. Loss-of-function experiments show that AMOT mediates YAP activation by UCA1, as UCA1 enhances the AMOT-YAP interaction to promote YAP dephosphorylation and nuclear translocation. Together, we characterize UCA1 as a lncRNA regulator of Hippo-YAP signaling and highlight the UCA1-AMOT-YAP signaling axis in ovarian cancer development.",

keywords = "Cancer Systems Biology, Omics, Proteomics, Systems Biology",

author = "Xianzhi Lin and Spindler, {Tassja J.} and {de Souza Fonseca}, {Marcos Abra{\~a}o} and Corona, {Rosario I.} and Seo, {Ji Heui} and Dezem, {Felipe Segato} and L. Li and Lee, {Janet M.} and Long, {Henry W.} and Sellers, {Thomas A.} and Karlan, {Beth Y.} and Houtan Noushmehr and Freedman, {Matthew L.} and Gayther, {Simon A.} and Kate Lawrenson",

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year = "2019",

month = jul,

day = "26",

doi = "10.1016/j.isci.2019.06.025",

language = "English (US)",

volume = "17",

pages = "242--255",

journal = "iScience",

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T1 - Super-Enhancer-Associated LncRNA UCA1 Interacts Directly with AMOT to Activate YAP Target Genes in Epithelial Ovarian Cancer

AU - Lin, Xianzhi

AU - Spindler, Tassja J.

AU - de Souza Fonseca, Marcos Abraão

AU - Corona, Rosario I.

AU - Seo, Ji Heui

AU - Dezem, Felipe Segato

AU - Li, L.

AU - Lee, Janet M.

AU - Long, Henry W.

AU - Sellers, Thomas A.

AU - Karlan, Beth Y.

AU - Noushmehr, Houtan

AU - Freedman, Matthew L.

AU - Gayther, Simon A.

AU - Lawrenson, Kate

PY - 2019/7/26

Y1 - 2019/7/26

N2 - Long noncoding RNAs (lncRNAs) have emerged as critical regulators of tumorigenesis, and yet their mechanistic roles remain challenging to characterize. Here, we integrate functional proteomics with lncRNA-interactome profiling to characterize Urothelial Cancer Associated 1 (UCA1), a candidate driver of ovarian cancer development. Reverse phase protein array (RPPA) analysis indicates that UCA1 activates transcription coactivator YAP and its target genes. In vivo RNA antisense purification (iRAP) of UCA1 interacting proteins identified angiomotin (AMOT), a known YAP regulator, as a direct binding partner. Loss-of-function experiments show that AMOT mediates YAP activation by UCA1, as UCA1 enhances the AMOT-YAP interaction to promote YAP dephosphorylation and nuclear translocation. Together, we characterize UCA1 as a lncRNA regulator of Hippo-YAP signaling and highlight the UCA1-AMOT-YAP signaling axis in ovarian cancer development.

AB - Long noncoding RNAs (lncRNAs) have emerged as critical regulators of tumorigenesis, and yet their mechanistic roles remain challenging to characterize. Here, we integrate functional proteomics with lncRNA-interactome profiling to characterize Urothelial Cancer Associated 1 (UCA1), a candidate driver of ovarian cancer development. Reverse phase protein array (RPPA) analysis indicates that UCA1 activates transcription coactivator YAP and its target genes. In vivo RNA antisense purification (iRAP) of UCA1 interacting proteins identified angiomotin (AMOT), a known YAP regulator, as a direct binding partner. Loss-of-function experiments show that AMOT mediates YAP activation by UCA1, as UCA1 enhances the AMOT-YAP interaction to promote YAP dephosphorylation and nuclear translocation. Together, we characterize UCA1 as a lncRNA regulator of Hippo-YAP signaling and highlight the UCA1-AMOT-YAP signaling axis in ovarian cancer development.

KW - Cancer Systems Biology

KW - Omics

KW - Proteomics

KW - Systems Biology

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Super-Enhancer-Associated LncRNA UCA1 Interacts Directly with AMOT to Activate YAP Target Genes in Epithelial Ovarian Cancer

Abstract

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