The epitranscriptome meets non-coding RNA: m6A-mediated regulation in oncogenesis and therapy

TL;DR

This review explores how m6A RNA modifications interact with non-coding RNAs to influence cancer development and treatment resistance.

Contribution

The paper highlights novel insights into the crosstalk between m6A modifications and non-coding RNAs in cancer progression and therapy.

Findings

m6A modifications regulate RNA stability and translation, impacting oncogene and tumor suppressor activity.

Non-coding RNAs influence m6A protein expression and vice versa, forming feedback loops in cancer.

m6A and ncRNA interactions affect the tumor microenvironment and immune responses, contributing to drug resistance.

Abstract

The field of epitranscriptomics discovered N6-methyladenosine (m6A) modifications, which function as fundamental elements that control RNA metabolism properties that powerfully affect cancer biology. This review examines the way m6A modifications shape RNA stability while regulating translation, together with their eraser and reader proteins. We demonstrate that m6A modifications guide oncogene and tumor suppressor transcript outcomes, which promote tumor growth, metastasis, and therapeutic resistance. The regulatory function of m6A depends significantly on its relationship with ncRNAs that mainly include miRNAs, lncRNAs, and circRNAs. The review examines the effects of m6A on ncRNA production, stability, export, and degradation, as well as the regulation of m6A protein expression by ncRNAs, highlighting intricate reciprocal feedback loops that drive cancer progression. The interplay between m6A RNA modifications and ncRNAs provides emerging evidence on how they collectively influence the tumor microenvironment, modulate immune system responses, and contribute to resistance. Harnessing ncRNA-m6A interactions for managing drug resistance offers promising therapeutic avenues. However, advancing our understanding of the context-specific roles of m6A modifications and translating these insights into clinical applications remains a significant challenge. This review synthesizes recent findings on ncRNA-m6A crosstalk to lay the groundwork for developing epitranscriptomic strategies in precision oncology.

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