Lung Cancer Chemoresistance: Insights into the Regulatory Role of lncRNAs

Abstract

Abstract Lung cancer remains the leading cause of cancer-related mortality worldwide, with chemoresistance being a major challenge in its treatment. Long non-coding RNAs (lncRNAs), a class of transcripts longer than 200 nucleotides without protein-coding potential, have emerged as critical regulators in tumour progression and drug resistance. This review systematically summarizes the multifaceted mechanisms through which lncRNAs influence chemoresistance across major lung cancer subtypes, particularly non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), including regulation of cell proliferation, cell cycle progression, migration, invasion, apoptosis, pyroptosis, necroptosis, and autophagy. Some key lncRNAs function as competing endogenous RNAs (ceRNAs) to sponge microRNAs, modulate chromatin architecture, or alter key signalling pathways (eg, PI3K/Akt, Wnt/β-catenin, and JAK2/STAT3), ultimately promoting survival and chemoresistance of lung cancer cells under chemotherapeutic stress. Clarification of these mechanisms provides novel insights into the development of early diagnostic markers and therapeutic targets. Future research should focus on elucidating specific lncRNA interactions, developing lncRNA-based therapeutics, and exploring their roles in tumour microenvironments and drug-resistant subpopulations to overcome chemoresistance.