Key Takeaways & Executive Findings
- •• m6A modifications on lncRNAs play pivotal roles in regulating tumor cell proliferation and apoptosis, offering potential targets for cancer therapy. • lncRNA m6A modifications significantly impact cancer cell migration, invasion, and metastasis, contributing to poor patient outcomes. • The interplay between m6A writers, erasers, and readers on lncRNAs modulates therapeutic resistance, presenting challenges and opportunities for overcoming drug resistance. • Targeting lncRNA m6A modifications holds promise for developing novel biomarkers and therapeutic interventions in oncology.
Abstract
Long non-coding RNAs (lncRNAs) are emerging as critical regulators of gene expression and cellular processes, and their N6-methyladenosine (m6A) modifications have been implicated in various cancers. This review synthesizes current knowledge on the functional roles of lncRNA m6A modifications in tumor proliferation, apoptosis, migration, invasion, metastasis, and therapeutic resistance. We discuss the molecular mechanisms by which m6A-modified lncRNAs influence cancer progression and highlight potential clinical applications. Understanding these pathways may pave the way for novel diagnostic and therapeutic strategies.
1. Introduction
Long non-coding RNAs (lncRNAs) are a class of transcripts longer than 200 nucleotides that do not encode proteins but regulate gene expression at various levels, including chromatin remodeling, transcription, and post-transcriptional processing. Emerging evidence has demonstrated that lncRNAs are frequently dysregulated in cancers and contribute to tumor initiation and progression. Among the numerous post-transcriptional modifications, N6-methyladenosine (m6A) is the most abundant internal modification in eukaryotic mRNAs and lncRNAs, dynamically regulated by methyltransferases ('writers'), demethylases ('erasers'), and binding proteins ('readers').
Recent studies have revealed that m6A modifications on lncRNAs play crucial roles in cancer biology by affecting RNA stability, splicing, export, and translation. Specifically, m6A-modified lncRNAs have been implicated in regulating key cellular processes such as proliferation, apoptosis, migration, invasion, and metastasis. Moreover, these modifications influence the response of cancer cells to therapeutic agents, contributing to drug resistance. Understanding the molecular mechanisms underlying lncRNA m6A modifications is essential for developing novel diagnostic biomarkers and targeted therapies.
This review aims to provide a comprehensive overview of the current knowledge on the role of lncRNA m6A modifications in cancer, focusing on their impact on tumor proliferation, apoptosis, migration, invasion, metastasis, and therapeutic resistance. We will also discuss the potential clinical implications and future research directions in this rapidly evolving field.
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Unknown (2026). The Role of lncRNA m6A Modifications in Tumor Proliferation, Apoptosis, Migration, Invasion, Metastasis, and Therapeutic Resistance. Acta Biochimica et Biophysica Sinica. https://doi.org/10.3724/abbs.2025134
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Frequently Asked Questions
What is the role of lncRNA m6A modifications in cancer proliferation?
m6A modifications on lncRNAs can regulate their stability and function, thereby influencing the expression of genes involved in cell cycle progression and proliferation. For example, m6A-modified lncRNAs may promote or suppress proliferation depending on the context, making them potential therapeutic targets.
How do lncRNA m6A modifications affect apoptosis?
m6A modifications can alter the expression of lncRNAs that modulate apoptotic pathways. By affecting the stability or translation of apoptosis-related genes, these modifications can either promote or inhibit apoptosis, contributing to tumor survival or death.
Can lncRNA m6A modifications influence metastasis?
Yes, m6A-modified lncRNAs have been shown to regulate genes involved in epithelial-mesenchymal transition (EMT), cell migration, and invasion, thereby promoting or suppressing metastasis. This highlights their potential as biomarkers for metastatic potential.
What is the significance of lncRNA m6A modifications in therapeutic resistance?
m6A modifications on lncRNAs can modulate the expression of drug resistance genes, affecting the sensitivity of cancer cells to chemotherapy, radiotherapy, and targeted therapy. Understanding these mechanisms may help overcome resistance and improve treatment outcomes.
Are there any clinical applications of lncRNA m6A modifications?
Yes, lncRNA m6A modifications hold promise as diagnostic and prognostic biomarkers, as well as therapeutic targets. Targeting the m6A machinery or specific m6A-modified lncRNAs could lead to novel cancer treatments, though more research is needed.
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