IDENTIFICATION AND CHARACTERIZATION OF REGULATORY NON-CODING RNAS IN THE HIPPO-YAP/TAZ SIGNALING PATHWAY

Abstract

Hippo-YAP/TAZ signaling is an evolutionarily conserved pathway regulating the expression of hundreds of genes involved in embryonic development, organ size control, and tumorigenesis. Among these genes, noncoding RNAs remain relatively underexplored. Utilizing gastric and non-small cell lung cancer models, I report the identification and functional characterization of a long noncoding RNA (lncRNA) and a microRNA (miRNA), namely SFTA1P and miR-582-5p, respectively. This study reports SFTA1P as a transcriptional target of YAP/TAZ/TEAD. SFTA1P is required for cell proliferation and tumorigenesis, and functions through targeting TAZ at the translational level. The dissertation also reports that miR-582-5p is positively regulated by YAP/TAZ. Functionally, miR-582-5p serves as a tumor-suppressive miRNA involved in the negative feedback regulation of Hippo-YAP/TAZ signaling. Altogether, the dissertation delineates the diverse roles of YAP/TAZ in the regulation of noncoding RNAs and the regulatory roles of these noncoding RNAs in fine-tuning Hippo-YAP/TAZ signaling in cancers.