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,
Lewyn Li,
Janet M. Lee,
Henry W. Long,
Thomas A. Sellers,
Beth Y. Karlan,
Houtan Noushmehr,
Matthew L. Freedman,
Simon A. Gayther,
Kate Lawrenson
Affiliations
Xianzhi Lin
Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
Tassja J. Spindler
Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
Marcos Abraão de Souza Fonseca
Department of Genetics, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil
Rosario I. Corona
Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Center for Bioinformatics and Functional Genomics, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
Ji-Heui Seo
Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA
Felipe Segato Dezem
Department of Genetics, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil
Lewyn Li
Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA
Janet M. Lee
Center for Bioinformatics and Functional Genomics, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
Henry W. Long
Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA, USA
Thomas A. Sellers
Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, FL, USA
Beth Y. Karlan
Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
Houtan Noushmehr
Department of Genetics, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil; Department of Neurosurgery, Henry Ford Health System, Detroit, MI, USA
Matthew L. Freedman
Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA, USA; The Eli and Edythe L. Broad Institute, Cambridge, MA, USA
Simon A. Gayther
Center for Bioinformatics and Functional Genomics, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
Kate Lawrenson
Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Center for Bioinformatics and Functional Genomics, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Corresponding author
Summary: 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. : Cancer Systems Biology; Omics; Proteomics; Systems Biology Subject Areas: Cancer Systems Biology, Omics, Proteomics, Systems Biology
