Long Non-Coding RNAs in Pathogenesis of Renal Cell Carcinoma: Epigenetic Regulation, Signaling Pathways, and Therapeutic Strategies.

Renal cell carcinoma (RCC) remains a major challenge in modern oncological urology, owing to its high heterogeneity, latent clinical course, and intrinsic resistance to chemotherapy and radiotherapy. In recent decades, the paradigm of carcinogenesis research has shifted from a primary focus on protein-coding genes alone to a broader investigation of the non-coding part of the transcriptome. Within this framework, long non-coding RNAs (lncRNAs) have emerged as fundamental regulators of cellular homeostasis. Accumulating evidence indicates that lncRNAs are not merely 'transcriptional noise' but components of intricate regulatory networks governing epigenetic, transcriptional, and post-transcriptional processes. Here, we present a comprehensive systematic review of the current literature addressing the role of lncRNA in the molecular pathogenesis of RCC. We discuss the roles of these molecules in key oncogenic signaling pathways, including PI3K/AKT/mTOR, Wnt/β-catenin, and Notch, and their contributions to tumor metabolic plasticity. The paper summarizes data on the link between lncRNAs and novel forms of regulated cell death-ferroptosis, cuproptosis, and disulphidosis. Particular attention is paid to their role in mediating resistance to tyrosine kinase inhibitors and their potential utility as highly specific biomarkers. Collectively, this review provides an updated perspective on the contribution of lncRNAs to RCC pathogenesis and outlines strategic directions for future research to support the development of more precise approaches in personalized oncology.