Regulatory subunits and post-translational modifications (PTMs) like acetylation, SUMOylation, and phosphorylation can further modulate the activity of m6A regulators, influencing their roles in cancer. For instance, acetylation of ALKBH5 by KAT8 enhances its demethylase activity, promoting tumorigenesis, while METTL3 activity can be regulated by SUMOylation, impacting cancer cell proliferation and metastasis.
The review also discusses the potential of targeting m6A regulators for cancer therapy. Small molecule inhibitors that target writers, erasers, and readers of m6A have shown promise in preclinical models. These inhibitors can modulate RNA metabolism, affecting processes like translation and decay, which in turn can inhibit cancer cell malignant phenotypes.
Beyond m6A, the review briefly touches on other RNA modifications such as m1A, m5C, m7G, m6Am, and ac4C, which also play significant roles in gene expression regulation. For example, m1A modification on mRNA is linked to stability and translation, with writers like TRMT6 and erasers like ALKBH3 implicated in cancer progression. Similarly, the m5C modification, regulated by writers like NSUN2 and erasers like TET1, affects RNA stability and translation, with potential roles in tumor development.
The review highlights the importance of understanding the complex interplay between different RNA modifications and their regulators in the context of cancer. It suggests that a systems biology approach could reveal how these modifications collaborate or compete with each other to influence cancer phenotypes. While research on m6A and its regulators is advanced, the study of other RNA modifications and their roles in cancer is still emerging, with much to be explored regarding their mechanisms and potential therapeutic implications.
In conclusion, the review provides a detailed overview of the current understanding of RNA modifications in cancer, emphasizing the potential of targeting these modifications for therapeutic intervention. It also points to the need for further research to uncover the full spectrum of regulatory mechanisms and their implications in cancer biology.
