# RNA Modification Related Diseases and Sensing Methods
## 3 RNA Modification and Cancer  
In several forms of cancer, a correlation has been observed between cancer malignancy and RNA modifications. METTL3 increases m6A levels in lung cancer, interacts with the translation initiation machinery to enhance mRNA translation, and activates hippo pathway effector transcription in human cancer cells through binding to the epidermal growth factor receptor and Post-synaptic density protein 95, Disc large homolog 1, and Zonula occludens-1 (PDZ) motifs. Moreover, it has been demonstrated that the mRNAs hippo pathway effector and transcriptional co-activator with PDZ-binding motif are among those that METTL3 helps to translate [56]. Based on this study, METTL3 may be a promising therapeutic target as it promotes the proliferation, survival, and invasion of human lung cancer cells (Figure 2) [56]. Hypoxia stimulates the expression of the m6A demethylase ALKBH5 and the 3\({}^{\prime}\)-UTR sequence AAACU, which have been found to decrease NANOG mRNA methylation levels, increase NANOG protein levels, and enhance stem cell populations in studies using human breast cancer cells (Figure 2) [57]. Hypoxia-inducible factor-1 (HIF-1a) and hypoxia-inducible factor-2 (HIF-2)-dependent mechanisms have also been shown to induce NANOG expression [57]. Another study found that, in breast cancer, exposure to hypoxia leads to m6A modification of the mRNAs encoding NANOG and Kruppel-like factor 4 (KLF4) being inhibited in a zinc finger protein 217 (ZNF217)-dependent manner [58]. ZNF217 or ALKBH5 may play a role in controlling the expression of pluripotency factors in breast cancer under hypoxic conditions [58]. Additionally, RNA modifications have been proposed to contribute to the malignant transformation of gastrointestinal malignancies. For example, it has been suggested that m6A modifications play a role in the malignant transformation of colorectal cancer [59]. The oncogene c-myc is implicated in the transcription of the M6A reader YTHDF1 in colorectal cancer, according to epigenetic data obtained by chromatin immunoprecipitation (Figure 2) [59]. YTHDF1 expression has been found to be related to various malignancy behaviors based on immunohistochemistry analysis of YTHDF1 expression and has been discovered to be an independent predictive factor in patients with colorectal cancer [59]. Case-control research on genetic alterations in pancreatic cancer has also revealed a link between FTO mutations and pancreatic cancer risk in Japan (Figure 2) [60]. Additionally, clear links between the FTO rs9939609 mutant polymorphism and endometrial and pancreatic cancer, particularly in Asian populations, have been established, suggesting that these markers could be used for early detection [61]. Malignant pleural mesothelioma risk has also been linked to the FTO rs9939609 mutation [62]. Another investigation into pancreatic cancer revealed that METTL3-deficient cells were more responsive to radiation, gemcitabine, and other anticancer medications such as 5-fluorouracil and cisplatin. Patients with pancreatic cancer may benefit from using METTL3 as a therapeutic agent since it is a potent target that boosts efficacy compared to other therapeutic agents [63]. Additionally, recent studies have demonstrated that m6A levels of miRNAs in the blood can accurately and sensitively identify stage I and stage II pancreatic cancer [64], making m6A levels a potentially novel yet valuable biomarker. Furthermore, numerous associations between RNA modifications and tumors and epithelial cancers have been reported. FTOs have been linked to acute myeloid leukemia (AML) (Figure 2), including mixed lineage leukemia (MLL) (Figure 2) with t (11q23) rearrangements, t (15; 17), involvement of the retinoic acid receptor-a (RARA), mutations in the FMS-like tyrosine kinase 3 (FLT3) gene with internal tandem duplication (ITD) mutations, and nucleophosmin 1 (NPM1) mutations. In a recent study, FTO was used as a therapeutic method against AML cells.