REVIEW: Mechanisms of Ferroptosis and Non-Coding RNAs in Non-Small Cell Lung Cancer

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Alena D. Selezneva¹, Alexey M. Burdennyy^1,2,a*, Anna D. Selezneva¹, Elena A. Filippova¹, Svetlana S. Lukina¹, Eleonora A. Braga¹, and Vitaliy I. Loginov¹

¹Research Institute of General Pathology and Pathophysiology, 125315 Moscow, Russia

²N. M. Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, 119334 Moscow, Russia

^* To whom correspondence should be addressed.

Received: July 21, 2025; Revised: October 2, 2025; Accepted: October 8, 2025

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Ferroptosis is an iron-dependent form of regulated cell death induced by hyperoxidation of polyunsaturated fatty acids (PUFAs) in cytoplasmic membrane phospholipids. Recent research has identified four key regulatory pathways of this process, with glutathione pathway (SLC7A11/SLC3A2)/GSH/GPX4 being the most central and well-studied. Functioning of all ferroptosis control systems is supported by the multilevel network of protein-coding and regulatory genes, whose dysregulated expression could trigger tumor cell transformation. Ferroptosis, alongside with other types of programmed cell death, plays a pivotal role in pathogenesis of many cancers, including non-small cell lung cancer (NSCLC). This review provides a comprehensive overview of the molecular mechanisms of ferroptosis and summarizes experimental evidence demonstrating involvement of the ferroptosis-associated non-coding RNAs (microRNAs and long non-coding RNAs) in the development and progression of NSCLC. Special emphasis is placed on the potential application of anti-ferroptotic and pro-ferroptotic non-coding RNAs in NSCLC therapy, focusing on targeted modulation of their expression to induce ferroptosis in tumor cells.

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KEY WORDS: ferroptosis, lipid peroxidation, non-coding RNA, long non-coding RNA, microRNA, non-small cell lung cancer

DOI: 10.1134/S0006297925602266

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