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  • Mechanistic Insights into Long Non-coding RNA-Mediated Gene Regulation Across Human Diseases

  • Elena Bagherizadeh,1 Mahtab Maleki,2,*
    1. Islamic Azad University; Science and Research Branch
    2. Islamic Azad University; Science and Research Branch


  • Introduction: Long non-coding RNAs (lncRNAs) are transcripts longer than 200 nucleotides that generally lack protein-coding capacity, although some can encode functional micropeptides. Most lncRNAs are transcribed by RNA polymerase II and undergo capping, splicing, and polyadenylation. They regulate gene expression at multiple levels, including transcription, mRNA stability, translation, and cellular localization, with functions often dependent on cell and tissue context. Dysregulated lncRNAs contribute to cancer, cardiovascular, neurological, and metabolic disorders. They also interact with epigenetic mechanisms, including DNA methylation, while methylation of lncRNA promoters can regulate their expression. This review summarizes lncRNA-mediated gene regulation, their roles in disease, and their therapeutic potential.
  • Methods: A literature review was conducted using PubMed and Google Scholar. Relevant research and review articles published from 2020 to 2026 were identified using terms including “lncRNA,” “gene regulation,” “epigenetic regulation,” “DNA methylation,” and “human diseases.” Studies were selected based on their relevance to lncRNA-mediated regulation and disease pathogenesis.
  • Results: lncRNAs regulate gene expression through transcriptional control, interactions with epigenetic factors, modulation of mRNA stability and translation, and regulation of protein localization. Their functions vary across cellular and tissue contexts. Dysregulation has been associated with abnormal proliferation, tumor progression, metastasis, and therapy resistance, particularly in cancer. lncRNAs also interact with DNA methylation-related factors and may influence methylation patterns, while promoter methylation can alter lncRNA expression. Overall, lncRNAs participate in complex regulatory networks linking gene expression to disease-related cellular processes.
  • Conclusion: Although substantial progress has been made, the functions and mechanisms of many lncRNAs remain incompletely understood. Their regulatory roles and interactions with epigenetic pathways, particularly DNA methylation, make them important contributors to human disease and potential therapeutic targets. Further studies are needed to clarify tissue-specific functions and mechanisms and to establish their clinical and therapeutic utility.
  • Keywords: Long non-coding RNA; gene regulation; DNA methylation; human diseases; therapeutic potential

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