Exploring the role of long non-coding RNAs in renal cell carcinoma: insights into signaling pathways

Abstract

Renal cell carcinoma (RCC), the most common type of kidney cancer, is characterized by a poor prognosis due to its aggressive metastasis and resistance to treatment. Long non-coding RNAs (lncRNAs) have emerged as key regulators of RCC progression, influencing cellular processes such as proliferation, migration, invasion, and apoptosis. LncRNA biogenesis occurs through both canonical and non-canonical pathways, involving RNA Polymerase II-mediated transcription and alternative splicing. LncRNAs like HOTAIR, MALAT1, and GAS5 regulate critical signaling pathways, including the PI3K/AKT/mTOR axis, Wnt/β-catenin, and JAK/STAT, while others, such as RCAT1, DUXAP9, and Lnc-LSG1, modulate protein degradation, impacting tumor growth and metastasis. Additionally, lncRNAs like EGFR-AS1 and MALAT1 enhance the EGFR/AKT and VEGF/Akt pathways, driving RCC cell proliferation and migration. LncRNAs such as HOTAIR and TCL6 also promote epithelial-to-mesenchymal transition, contributing to tumor invasion and therapy resistance. Furthermore, lncRNAs regulate the p53 pathway, with some, like MEG3, acting as tumor suppressors, while others, like SNHG3, suppress p53 activity, accelerating RCC progression. These insights into lncRNA-mediated regulatory mechanisms provide promising therapeutic targets for RCC, suggesting that modulating specific lncRNAs or their associated pathways could offer innovative strategies for treatment and prognosis. This review presents a comprehensive analysis of the biogenesis, functions, and regulatory roles of lncRNAs in RCC, emphasizing their potential as diagnostic biomarkers and therapeutic targets to improve patient outcomes.