Targeting the LncRNA–Hippo axis in cancer with plant-derived compounds

Long non-coding RNAs (lncRNAs) have emerged as pivotal regulators of gene expression, playing essential roles in cancer initiation, progression, metastasis, and therapy resistance. Accumulating evidence indicates that lncRNAs interact closely with the Hippo signaling pathway, a key regulator of cell proliferation, apoptosis, and tissue homeostasis, whose dysregulation is frequently associated with tumor development. Recent studies have highlighted the potential of plant-derived phytochemicals to modulate lncRNA expression and influence Hippo pathway activity. Well-known compounds such as curcumin, resveratrol, quercetin, and berberine can regulate both oncogenic and tumor-suppressive lncRNAs, thereby affecting YAP/TAZ signaling and tumor progression. Despite promising preclinical findings, clinical translation remains limited due to poor bioavailability and stability of many phytochemicals. Nanotechnology-based delivery systems offer a promising solution by enhancing compound stability and targeted delivery. Collectively, these findings suggest that phytochemical-mediated modulation of the lncRNA–Hippo signaling axis could represent a novel and effective strategy for future cancer therapies.