<p>The Potential Role of N6-Methyladenosine (m6A) Demethylase Fat Mass and Obesity-Associated Gene (FTO) in Human Cancers</p>

Abstract

N6-methyladenosine (m6A) demethylase fat mass and obesity-associated gene ( FTO ), previously recognized to be related with obesity and diabetes, was gradually discovered to be dysregulated in multiple cancers and plays an oncogenic or tumor-suppressive role. However, the specific expression and pro- or anti-cancer role of FTO in various cancers remained controversial. In this review, through summarizing the available literature, we found that FTO single nucleotide polymorphisms (SNPs) were closely related with cancer risk. Additionally, the dysregulation of FTO was implicated in multiple biological processes, such as cancer cell apoptosis, proliferation, migration, invasion, metastasis, cell-cycle, differentiation, stem cell self-renewal and so on. These modulations mostly relied on the communications between FTO and specific signaling pathways, including PI3K/AKT , MAPK and mTOR signaling pathways. Furthermore, FTO had great potential for clinical application by serving as a prognostic biomarker.

Immunotherapeutic Potential of m6A-Modifiers and MicroRNAs in Controlling Acute Myeloid Leukaemia

“…Likewise, m6A-methylases (writer), m6A-demethylases FTO, and ALKBH5 (eraser) have also been found to be aberrantly expressed in APL and LSCs/LICs and promote leukemogenesis by targeting ASB2, RARA, LILRB4, CEBPA, TACC3, Myc, and the P-21 gene [ 51 ]. Nevertheless, FTO single nucleotide polymorphisms have been also found to be associated with other cancers [ 119 ]. Likewise, the reader protein ‘YTHDF2′ has been also found to promote leukemogenesis by inhibiting its targets Tla1 [ 53 ] and TNF-α [ 54 ] through universal YTHDF2-mediated mRNA decay mechanisms [ 58 ].…”

Lifetime Impact of Cow’s Milk on Overactivation of mTORC1: From Fetal to Childhood Overgrowth, Acne, Diabetes, Cancers, and Neurodegeneration

“…FTO is a N6-methyladenosine (m6A) demethylase, which controls the expression of several components of the mTORC1 pathway [ 180 , 181 , 182 , 183 ]. Milk via miR-148a-, miR-21- and miR-29b-mediated suppression of DNMTs may promote CpG demethylation at intron 1 of FTO increasing FTO expression amplifying the m6A-regulated transcriptional machinery for postnatal growth [ 184 ].…”

N6‐methyladenosine Steers RNA Metabolism and Regulation in Cancer

“…Pei et al [162] also detected elevated m 6 A level in the peripheral blood leukocyte from non-small cell lung cancer patients by flow cytometry, indicating the potential use of m 6 A as a non-invasive biomarker. Furthermore, m 6 A regulators, including METTL3 [77,[163][164][165][166][167][168][169], WTAP [170][171][172][173], FTO [174][175][176][177], IGF2BPs [178][179][180][181][182][183][184], and YTHDFs [73,[185][186][187][188][189][190][191][192], have been proven to associate with favorable or unfavorable prognosis in different types of cancers (detailed in Section 3). It should be noted that prognosis is not simply associated with the expression of a certain gene but a comprehensive signature of multiple m 6 A regulators in cancers, including lung cancer [163,164], pancreatic cancer [166,193], and HCC [194].…”