The regulatory role and therapeutic potential of long non-coding RNA in non-small cell lung cancer

Lung cancer remains the leading cause of cancer-related mortality worldwide, with non-small cell lung cancer (NSCLC) being the predominant subtype. Recent advances in transcriptome sequencing have highlighted the critical role of long non-coding RNAs (lncRNAs) in NSCLC, with lncRNAs influencing gene expression through epigenetic, transcriptional, and post-transcriptional mechanisms. Despite the growing understanding of lncRNAs, challenges such as delayed diagnosis and drug resistance continue to complicate NSCLC management. This review explores novel findings in the role of lncRNAs (e.g., MALAT1, HOTAIR, and GAS5) in NSCLC, with a particular focus on their encoded small peptides and N6-methyladenosine (m6A) modifications. We further discuss how the interplay between lncRNAs, their encoded peptides, and m6A modifications can provide new strategies for improving NSCLC diagnosis, treatment, and overcoming drug resistance. This review also highlights emerging research avenues that could lead to innovative clinical interventions in NSCLC.