Regulatory role and mechanism of m6A RNA modification in human metabolic diseases

Abstract

Metabolic diseases caused by disorders in amino acids, glucose, lipid metabolism, and other metabolic risk factors show high incidences in young people, and current treatments are ineffective. N 6 -methyladenosine (m 6 A) RNA modification is a posttranscriptional regulation of gene expression with several effects on physiological processes and biological functions. Recent studies report that m 6 A RNA modification is involved in various metabolic pathways and development of common metabolic diseases, making it a potential disease-specific therapeutic target. This review explores components, mechanisms, and research methods of m 6 A RNA modification. In addition, we summarize the progress of research on m 6 A RNA modification in metabolism-related human diseases, including diabetes, obesity, non-alcoholic fatty liver disease, osteoporosis, and cancer. Furthermore, opportunities and the challenges facing basic research and clinical application of m 6 A RNA modification in metabolism-related human diseases are discussed. This review is meant to enhance our understanding of the molecular mechanisms, research methods, and clinical significance of m 6 A RNA modification in metabolism-related human diseases.

Potential genetic therapies based on m6A methylation for skin regeneration: Wound healing and scars/keloids

“…The biological function of m6A modification is primarily mediated through the specific recognition and binding of readers, which are responsible for the diverse effects of m6A methylation on gene expression ( Huang et al, 2020 ; Zhang et al, 2021b ). These effects include the regulation of RNA splicing, output, decay, stabilization, and translation ( Wang et al, 2014 ; Alarcon et al, 2015 ; Spitale et al, 2015 ; Xiao et al, 2016 ; Roundtree et al, 2017b ; Slobodin et al, 2017 ).…”

Pseudorabies virus exploits N6-methyladenosine modification to promote viral replication

“…N 6 -methyladenosine modification regulates various cellular physiological processes such as cell autophagy (Jin et al, 2018), cell differentiation and development (Frye et al, 2018), embryonic stem cells (ESCs) tumorigenicity (Sun et al, 2021), signal transduction (Chen et al, 2019), transcription and chromatin state (Wei and He, 2021) and immune response (Ma et al, 2021;Dong et al, 2022). Not only that, m 6 A modification has also been implicated in many pathological processes, such as human metabolic diseases (Zhang et al, 2021), cardiovascular diseases (Yankova et al, 2021;Zhou et al, 2021a), Alzheimer's disease (AD; Shafik et al, 2021), cancer (Zhou et al, 2021b) and viral infections (Yu et al, 2021). The majority of current studies on m 6 A modification and viral infection are related to human pathogenic viruses, especially oncogenic viruses, and there have been many studies on the regulatory effects of m 6 A modification on viruses of the Herpesviridae family.…”

A cleaved METTL3 potentiates the METTL3-WTAP interaction and breast cancer progression

“…m 6 A mRNA modification participates in numerous physiological processes, such as neurogenesis (Li et al, 2017b; Li et al, 2018b; Livneh et al, 2020; Wang et al, 2018; Yoon et al , 2017), embryo development (Batista et al, 2014; Li et al, 2018a; Mendel et al , 2018; Wang et al , 2014), and reproductive system development (Haussmann et al , 2016; Ivanova et al , 2017; Kasowitz et al, 2018; Xia et al, 2018; Zheng et al , 2013). Dysregulation of m 6 A deposition is associated with various diseases including cancer pathogenesis and drug resistance (Huang et al, 2020; Lan et al, 2021; Zhang et al, 2021), such as the core m 6 A methyltransferase (METTL3) promotes the progression of breast cancer through elevating expression of mammalian hepatitis BX-interacting protein and inhibiting tumor suppressor let-7g (Cai et al , 2018), inhibits tumor immune surveillance by upregulating PD-L1 mRNA level (Wan et al , 2022), and contributes to breast cancer tamoxifen resistance by upregulation of AK4 expression (Liu et al , 2020).…”