Noncoding RNAs as mechanistic regulators and therapeutic modulators of YAP/TAZ signaling in colorectal cancer.

Abstract

Colorectal cancer (CRC) continues to represent a significant global health challenge due to its high incidence and mortality rates. Among the signaling pathways implicated in CRC, the Hippo pathway has gained considerable attention for its evolutionarily conserved role in regulating cellular proliferation, programmed cell death, and organ size control. The recent studies have revealed that alterations in this pathway contribute not only to tumor initiation but also to metastasis and therapy resistance. Emerging evidence underscores the pivotal involvement of noncoding RNAs (ncRNAs)-including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs)-in modulating this pathway, particularly through the regulation of its core effectors, Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ). The intricate crosstalk between ncRNAs and Hippo signaling components suggests a multilayered regulatory mechanism that warrants further investigation. This review provides mechanistic insights into the dynamic crosstalk between ncRNAs and the YAP/TAZ axis, highlighting their roles in tumor progression, metastasis, and chemoresistance. Considering these intricate interactions, this review further emphasizes the emerging therapeutic and biomarker potential of ncRNAs, offering novel perspectives for both targeted intervention and early diagnosis in CRC management.