Targeting the lncRNA PVT-1-Hippo signaling axis in kidney diseases: an emerging therapeutic paradigm

Globally, the number of patients suffering from a diverse spectrum of kidney diseases, including parenchymal acute kidney injury (AKI), chronic kidney diseases (CKD), which includes diabetic kidney disease (DKD), and other chronic nephropathies, along with malignant renal cell carcinoma (RCC), is rising rapidly. Although they exhibit clinical heterogeneity, these conditions share common pathomechanisms, including tubular epithelial injury, inflammation, and progressive fibrosis, yet lack unified pharmacological targets that can address this spectrum simultaneously. Among these pathways, the Hippo signaling pathway has emerged as a key regulator of renal tissue homeostasis, epithelial plasticity, and fibrotic remodeling. Additionally, long non-coding RNAs (lncRNAs) are emerging coordinators of renal injury responses, with plasmacytoma variant translocation-1 (PVT-1) gaining significant attention as a pleiotropic renal disease transcript. Growing evidence indicates that lncRNA PVT-1 is dysregulated in conditions of intrinsic parenchymal kidney diseases as well as malignant tumors, and that it contributes to inflammatory signaling, tubular injury, extracellular matrix deposition, oxidative stress, and abnormal cellular proliferation. Thus, lncRNA PVT-1 may serve as a context-dependent therapeutic target across a variety of diseases. However, the precise regulatory role of lncRNA PVT-1 in Hippo signaling in the context of kidney diseases remains poorly understood. Hence, this review summarizes the role of lncRNA PVT-1 in renal physiology and various pathologies, discusses the growing role of Hippo signaling in kidney homeostasis, proposes a mechanistic framework linking lncRNA PVT-1 to Hippo-mediated kidney injury, addresses emerging pharmacological strategies, including CRISPR technologies targeting this axis, and explores its biomarker potential to diagnose and mitigate various kidney diseases.