Crosstalk Between Noncoding Rnas and Autophagy in Renal Cell Carcinoma: Deciphering Molecular Pathways and Therapeutic Prospects Publisher



Ma Alimohammadi Mina AMIN ; M Noroozi MOJGAN ; A Mafi ALIREZA ; NULL ; A Abbasi AMIRHOSEIN ; N Farahani NAJMA ; Sm Khoshnazar Seyedeh MAHDIEH ; M Hashemi MEHRDAD ; A Taheriazam AFSHIN ; K Hushmandi KIAVASH
Source: Cancer Cell International Published:2025

Abstract

Renal cell carcinoma (RCC) is one of the most common and aggressive forms of kidney cancer, accounting for over 90% of cases. Despite advances in diagnosis and treatment, RCC is often detected at advanced stages and demonstrates poor response to traditional therapies such as chemotherapy, radiotherapy, and hormonal treatment. Consequently, novel molecular targets are urgently needed. Autophagy, a tightly regulated catabolic mechanism that preserves cellular homeostasis via degradation of damaged organelles and proteins, plays a dual role in RCC—acting both as a tumor suppressor in early stages and a tumor promoter under stress conditions. Recent studies have revealed that non-coding RNAs (ncRNAs), particularly long ncRNAs and microRNAs (miRNAs), are key regulators of autophagy in various cancers, including RCC. These ncRNAs influence the expression of autophagy-related genes and modulate critical signaling pathways such as PI3K/AKT/mTOR, AMPK, p53, and KEAP1/NRF2. By acting as molecular sponges, scaffolds, and transcriptional regulators, ncRNAs either enhance or suppress autophagic activity, thereby affecting tumor progression, metastasis, and treatment resistance. This review synthesizes current knowledge on the crosstalk between ncRNAs and autophagy in RCC. We identify specific ncRNAs involved in RCC pathogenesis, describe their regulatory mechanisms, and evaluate their potential as diagnostic biomarkers and therapeutic targets. Understanding these complex molecular interactions may lead to more effective, personalized treatment strategies and improved clinical outcomes for RCC patients. © 2025 Elsevier B.V., All rights reserved.