Brain tumor
Glioblastoma multiforme (GBM) is the most aggressive (grade IV) and most common form of a malignant brain tumor. Even when aggressive multimodality therapy consisting of radiotherapy, chemotherapy, and surgical excision is used, median survival is only 12–17 months. Standard therapy for glioblastoma multiforme consists of maximal surgical resection of the tumor, followed by radiotherapy between two and four weeks after the surgical procedure to remove the cancer, then by chemotherapy, such as temozolomide. Most patients with glioblastoma take a corticosteroid, typically dexamethasone, during their illness to relieve symptoms. Experimental treatments include targeted therapy, gamma knife radiosurgery, boron neutron capture therapy and gene therapy.
N6-Methyladenosine
Considering the versatile functions of mA in various physiological processes, it is thus not surprising to find links between mA and numerous human diseases; many originated from mutations or single nucleotide polymorphisms (SNPs) of cognate factors of mA. The linkages between mA and numerous cancer types have been indicated in reports that include stomach cancer, prostate cancer, breast cancer, pancreatic cancer, kidney cancer, mesothelioma, sarcoma, and leukaemia. The impacts of mA on cancer cell proliferation might be much more profound with more data emerging. The depletion of METTL3 is known to cause apoptosis of cancer cells and reduce invasiveness of cancer cells, while the activation of ALKBH5 by hypoxia was shown to cause cancer stem cell enrichment. mA has also been indicated in the regulation of energy homeostasis and obesity, as FTO is a key regulatory gene for energy metabolism and obesity. SNPs of "FTO" have been shown to associate with body mass index in human populations and occurrence of obesity and diabetes. The influence of FTO on pre-adipocyte differentiation has been suggested. The connection between mA and neuronal disorders has also been studied. For instance, neurodegenerative diseases may be affected by mA as the cognate dopamine signalling was shown to be dependent on FTO and correct mA methylation on key signalling transcripts. The mutations in HNRNPA2B1, a potential reader of mA, have been known to cause neurodegeneration. The IGF2BP1–3, a novel class of mA reader, has oncogenic functions. IGF2BP1–3 knockdown or knockout decreased MYC protein expression, cell proliferation and colony formation in human cancer cell lines. The ZC3H13,a member of the m6A methyltransferase complex, markedly inhibited the colorectal cancer cells growth when knocked down.