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

Authors

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

Recommended Citation

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, and Lawrenson K. Super-Enhancer-Associated LncRNA UCA1 Interacts Directly with AMOT to Activate YAP Target Genes in Epithelial Ovarian Cancer. iScience 2019; 17:242-255.

Document Type

Article

Publication Date

7-26-2019

Publication Title

iScience

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.

Comments

original version available at: https://doi.org/10.1016/j.isci.2019.06.025. Creative Commons Attribution License

PubMed ID

31307004

Volume

17

First Page

242

Last Page

255