Functions, mechanisms, and therapeutic implications of METTL14 in human cancer

Abstract

RNA modification plays a crucial role in many biological functions, and its abnormal regulation is associated with the progression of cancer. Among them, N6-methyladenine (m6A) is the most abundant RNA modification. Methyltransferase-like 14 (METTL14) is the central component of the m6A methylated transferase complex, which is involved in the dynamic reversible process of m6A modification. METTL14 acts as both an oncogene and tumor suppressor gene to regulate the occurrence and development of various cancers. The abnormal m6A level induced by METTL14 is related to tumorigenesis, proliferation, metastasis, and invasion. To date, the molecular mechanism of METTL14 in various malignant tumors has not been fully studied. In this paper, we systematically summarize the latest research progress on METTL14 as a new biomarker for cancer diagnosis and its biological function in human tumors and discuss its potential clinical application. This study aims to provide new ideas for targeted therapy and improved prognoses in cancer.

N6-methyladenosine methyltransferase KIAA1429 elevates colorectal cancer aerobic glycolysis via HK2-dependent manner

“…N 6 -methyladenosine (m 6 A), one of the common epitranscriptomic modifications in eukaryotic mRNA, is an emerging and increasing field for cancer [ 20 , 21 ]. The m 6 A could be installed by m 6 A methyltransferase complex, containing methyltransferase-like 3 (METTL3), METTL14 and Wilms tumor 1-associated protein (WTAP).…”

The role, mechanism, and application of RNA methyltransferase METTL14 in gastrointestinal cancer

“…m6A modification exists in nearly all eukaryotes and in a part of viruses, yeasts, bacteria, and plants [ 12 ]. m6A binding sites are found in the RRACH sequence ( R = A/G, H = A/C/U) and are mainly enriched in the 3’ untranslated regions (UTRs) near the stop codon of mRNA exon [ 12 , 15 ]. Remarkably, m6A mediated-RNA epigenetics modification plays an important role in controlling physiological activities, such as embryonic stem cell differentiation, DNA repair, meiosis, tissue remodeling, and circadian rhythm, etc.…”

“…As the homologue of FTO, ALKBH3 and ALKBH5 principally mediate the transport, metabolism, and assembly of mRNA [ 46 – 48 ]. These erasers promote the transformation of m6A into N6-hydroxymethyladeosine and N6-formyladenosine successively, which is finally hydrolyzed into adenosine [ 12 , 17 ].…”

“…Recently, mounting studies have identified more than 100 kinds of chemical modifications in RNA, which exploits a new research field of epigenetic regulation controlled by RNA modification [9][10][11]. RNA methylation is the main form of RNA modifications, including N6-methyladenosine (m6A), m1A, 1-methylguanosine (m1G), m2G, m6G, m7G, 5-methylcytosine (m5C), 2ʹ-O-methylation (Nm), pseudouridine (Ψ) and Inosine (I), among which m6A modification is the most abundant kind accounting for approximately half of all RNA methylation modifications [5,[12][13][14]. m6A modification exists in nearly all eukaryotes and in a part of viruses, yeasts, bacteria, and plants [12].…”

“…RNA methylation is the main form of RNA modifications, including N6-methyladenosine (m6A), m1A, 1-methylguanosine (m1G), m2G, m6G, m7G, 5-methylcytosine (m5C), 2ʹ-O-methylation (Nm), pseudouridine (Ψ) and Inosine (I), among which m6A modification is the most abundant kind accounting for approximately half of all RNA methylation modifications [5,[12][13][14]. m6A modification exists in nearly all eukaryotes and in a part of viruses, yeasts, bacteria, and plants [12]. m6A binding sites are found in the RRACH sequence (R = A/G, H = A/C/U) and are mainly enriched in the 3' untranslated regions (UTRs) near the stop codon of mRNA exon [12,15].…”