Alimohammadi Mina, Noroozi Mojgan, Mafi Alireza, Zare Khormizi Fateme, Abbasi Amirhosein, Farahani Najma, Khoshnazar Seyedeh Mahdieh, Hashemi Mehrdad, Taheriazam Afshin, Hushmandi Kiavash
Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Molecular Medicine Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.
Cancer Cell Int. 2025 Sep 2;25(1):318. doi: 10.1186/s12935-025-03957-x.
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.
肾细胞癌（RCC）是最常见且侵袭性最强的肾癌形式之一，占所有肾癌病例的90%以上。尽管在诊断和治疗方面取得了进展，但RCC往往在晚期才被发现，并且对化疗、放疗和激素治疗等传统疗法反应不佳。因此，迫切需要新的分子靶点。自噬是一种严格调控的分解代谢机制，通过降解受损的细胞器和蛋白质来维持细胞内稳态，在RCC中发挥双重作用——在早期作为肿瘤抑制因子，在应激条件下作为肿瘤促进因子。最近的研究表明，非编码RNA（ncRNA），特别是长链ncRNA和微小RNA（miRNA），是包括RCC在内的各种癌症中自噬的关键调节因子。这些ncRNA影响自噬相关基因的表达，并调节PI3K/AKT/mTOR、AMPK、p53和KEAP1/NRF2等关键信号通路。通过充当分子海绵、支架和转录调节因子，ncRNA增强或抑制自噬活性，从而影响肿瘤进展、转移和治疗耐药性。本综述综合了目前关于RCC中ncRNA与自噬之间相互作用的知识。我们确定了参与RCC发病机制的特定ncRNA，描述了它们的调节机制，并评估了它们作为诊断生物标志物和治疗靶点的潜力。了解这些复杂的分子相互作用可能会为RCC患者带来更有效、个性化的治疗策略，并改善临床结果。
