Abstract
Accumulating lines of evidence indicate that the deregulation of m6A is involved in various cancer types. The m6A RNA methylation is modulated by m6A methyltransferases, demethylases, and reader proteins. Although the aberrant expression of m6A RNA methylation contributes to the development and progression of multiple cancer types, the roles of m6A regulators across numerous types of cancers remain largely unknown. Here, we comprehensively investigated the expression, genetic alteration, and prognosis significance of 20 commonly studied m6A regulators across diverse cancer types using TCGA datasets via bioinformatic analyses. The results revealed that the m6A regulators exhibited widespread dysregulation, genetic alteration, and the modulation of oncogenic pathways across TCGA cancer types. In addition, most of the m6A regulators were closely relevant with significant prognosis in many cancer types. Furthermore, we also constructed the protein–protein interacting network of the 20 m6A regulators, and a more complex interacting regulatory network including m6A regulators and their corresponding interacting factors. Besides, the networks between m6A regulators and their upstream regulators such as miRNAs or transcriptional factors were further constructed in this study. Finally, the possible chemicals targeting each m6A regulator were obtained by bioinformatics analysis and the m6A regulators–potential drugs network was further constructed. Taken together, the comprehensive analyses of m6A regulators might provide novel insights into the m6A regulators’ roles across cancer types and shed light on their potential molecular mechanisms as well as help develop new therapy approaches for cancers.
Highlights
A variety of biological processes are orchestrated by posttranscriptional modifications including RNA modifications (Zhao et al, 2017)
By searching the GSCALite database, we found that the expressions of many m6A methylation regulators were changed across multiple cancer types (Figure 1C)
The results revealed that the levels of IGF2BP1, IGF2BP2 and IGF2BP3, were remarkably upregulated in many cancer types such as bladder urothelial carcinoma (BLCA), liver hepatocellular carcinoma (LIHC), lung adenocarcinoma (LUAD), and lung squamous cell carcinoma (LUSC) (Figure 1D)
Summary
A variety of biological processes are orchestrated by posttranscriptional modifications including RNA modifications (Zhao et al, 2017). The erasers, being discovered in the cellular nuclei, are m6A demethylase enzymes such as FTO and ALKBH5, which remove the m6A and result in reducing the m6A levels (Zhang et al, 2017). The readers such as IGF2BP1 and RBMX, distributing in both cellular nuclei and cytoplasm, can decode the m6A methylation information via binding to the m6A sites and further initiate the different downstream signals (Sun et al, 2019). Recent studies had demonstrated that the decreased RNA methylation of critical genes in β-cell markedly contributed to the pathophysiology of human T2D (De Jesus et al, 2019)
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