LncRNA SFTA1P mediates positive feedback regulation of the Hippo-YAP/TAZ signaling pathway in non-small cell lung cancer

Long non-coding RNAs (lncRNAs) regulate numerous biological processes involved in both development and carcinogenesis. Hippo-YAP/TAZ signaling, a critical pathway responsible for organ size control, is often dysregulated in a variety of cancers. However, the nature and function of YAP/TAZ-regulated lncRNAs during tumorigenesis remain largely unexplored. By profiling YAP/TAZ-regulated lncRNAs, we identified SFTA1P as a novel transcriptional target and a positive feedback regulator of YAP/TAZ signaling. Using non-small cell lung cancer (NSCLC) cell lines, we show that SFTA1P is transcriptionally activated by YAP/TAZ in a TEAD-dependent manner. Functionally, knockdown of SFTA1P in NSCLC cell lines inhibited proliferation, induced programmed cell death, and compromised their tumorigenic potential. Mechanistically, SFTA1P knockdown decreased TAZ protein abundance and consequently, the expression of YAP/TAZ transcriptional targets. We provide evidence that this phenomenon could potentially be mediated via its interaction with TAZ mRNA to regulate TAZ translation. Our results reveal SFTA1P as a positive feedback regulator of Hippo-YAP/TAZ signaling, which may serve as the molecular basis for lncRNA-based therapies against YAP/TAZ-driven cancers.

Automated summary

Long non-coding RNAs (lncRNAs) play critical roles in development and carcinogenesis, while the Hippo-YAP/TAZ signaling pathway is essential for organ size control and often dysregulated in cancers. SFTA1P was identified as a novel transcriptional target and positive feedback regulator of YAP/TAZ signaling, with knockdown inhibiting proliferation and inducing cell death in NSCLC cell lines. Mechanistically, SFTA1P knockdown decreased TAZ protein abundance, affecting the expression of YAP/TAZ transcriptional targets, suggesting its potential role in lncRNA-based therapies against YAP/TAZ-driven cancers.