m6A methylation: a process reshaping the tumour immune microenvironment and regulating immune evasion

Abstract

N6-methyladenosine (m6A) methylation is the most universal internal modification in eukaryotic mRNA. With elaborate functions executed by m6A writers, erasers, and readers, m6A modulation is involved in myriad physiological and pathological processes. Extensive studies have demonstrated m6A modulation in diverse tumours, with effects on tumorigenesis, metastasis, and resistance. Recent evidence has revealed an emerging role of m6A modulation in tumour immunoregulation, and divergent m6A methylation patterns have been revealed in the tumour microenvironment. To depict the regulatory role of m6A methylation in the tumour immune microenvironment (TIME) and its effect on immune evasion, this review focuses on the TIME, which is characterized by hypoxia, metabolic reprogramming, acidity, and immunosuppression, and outlines the m6A-regulated TIME and immune evasion under divergent stimuli. Furthermore, m6A modulation patterns in anti-tumour immune cells are summarized.

System analysis identifies UBE2C as a novel oncogene target for adrenocortical carcinoma

“…M6A methylation can speed up transcription and participate in proteins translation and mRNA degradation [43][44][45]. m6A methylation modification can directly or indirectly regulate target genes, which can affect biological behaviors such as the proliferation, metastasis, and immune escape of tumor cells [46]. Hence, explaining the relationship between UBE2C and m6A regulators in ACC can enhance our understanding of the mechanism of UBE2C promoting the tumor development.…”

Significance of N6-methyladenosine RNA methylation regulators in diagnosis and subtype classification of primary Sjögren’s syndrome

“…Wang et al [ 48 ] found that m6A proteins affect tumour proliferation and metastasis in breast cancer and are strongly associated with patient prognosis. Cao et al [ 49 ] demonstrated the regulatory role of m 6 A methylation in the tumour immune microenvironment (TIME). These studies suggest that PSS as well as some malignant diseases can be treated by targeting m6A mRNA methylation.…”

Development of pharmacological immunoregulatory anti-cancer therapeutics: current mechanistic studies and clinical opportunities

“… 400 – 402 N6-methyladenosine (m6A) RNA modification, the most common RNA methylation, is closely associated with cancer progression, drug resistance 373 , 374 and cancer immunity. 403 – 405 Notably, antagonizing m6A modifiers can sensitize tumors to PD-1 blockade in mice. 406 – 410 However, most agents targeting m6A regulators are still in preclinical development and none has entered clinical evaluation.…”