The Roles of RNA N6-Methyladenosine in Regulating Stem Cell Fate

Abstract

RNA N6-methyladenosine (m6A) modification has important regulatory roles in determining cell fate. The reversible methylation process of adding and removing m6A marks is dynamically regulated by a fine-tuned coordination of many enzymes and binding proteins. Stem cells have self-renewal and pluripotent potential and show broad prospects in regenerative medicine and other fields. Stem cells have also been identified in cancer, which is linked to cancer metastasis, therapy resistance, and recurrence. Herein, we aimed to review the molecular mechanism that controls the reversible balance of m6A level in stem cells and the effect of m6A modification on the balance between pluripotency and differentiation. Additionally, we also elaborated the association between aberrant m6A modification and the maintenance of cancer stem cells in many cancers. Moreover, we discussed about the clinical implications of m6A modification in cancer stem cells for cancer diagnosis and therapy.

N6-methyladenosine (m6A) reader IGF2BP2 promotes gastric cancer progression via targeting SIRT1

“…Novel insights are inclined to propose new solutions based on epigenetics molecular mechanism. N [ 6 ]-methyladenosine (m 6 A) is one of the most common modifications of messenger RNAs (mRNAs) in eukaryotes [ 14 , 15 ]. Mountains of evidence have shown that m 6 A is involved in numerous pathophysiological process, including GC.…”

“…For the GC tumorigenesis, m 6 A participates in the progression [ 22 ]. For instance, m 6 A methyltransferase KIAA1429 catalyzes the m 6 A modification on LINC00958 loci and then LINC00958 interacts with GLUT1 mRNA through m [ 6 ]A-dependent manner to enhance GLUT1 mRNA transcript stability [ 23 ]. YTHDC2 recognizes the m [ 6 ]A-modified 5`-UTR of YAP mRNA to enhance the translation efficiency of YAP, and CRISPR-Cas9-mediated YTHDC2 knockout significantly inhibits the cell viability and proliferation of GC cells [ 24 ].…”

“…For instance, m 6 A methyltransferase KIAA1429 catalyzes the m 6 A modification on LINC00958 loci and then LINC00958 interacts with GLUT1 mRNA through m [ 6 ]A-dependent manner to enhance GLUT1 mRNA transcript stability [ 23 ]. YTHDC2 recognizes the m [ 6 ]A-modified 5`-UTR of YAP mRNA to enhance the translation efficiency of YAP, and CRISPR-Cas9-mediated YTHDC2 knockout significantly inhibits the cell viability and proliferation of GC cells [ 24 ]. METTL16 is highly expressed in GC cells and associated with prognosis, and METTL16 down-regulation inhibits the proliferation via G1/S blocking and reduces the level of cyclin D1 [ 25 ].…”

“…N [ 6 ]-Methyladenosine (m 6 A) is a critical chemical modification occurred on RNA. M 6 A is a reversible modification catalyzed by methyltransferase complexes (‘writers’), demethylase (‘erasers’) and binding proteins (‘readers’) [ 6–8 ]. METTL3, KIAA1429, WTAP, and METTL14 constitute the methyltransferase complex.…”

Role of m6A modification in female infertility and reproductive system diseases

“…For example, YTHDF1 promotes the translation of m6A modified mRNA, while YTHDF2 lowers mRNA stability, induces mRNA degradation, and mediates mRNA subcellular localization and selective splicing. (Figure 1) The other types of m6A protein machineries have been introduced in detail in a large number of reviews [19,20].…”