The biological function of m6A reader YTHDF2 and its role in human disease

Abstract

N6-methyladenosine (m6A) modification is a dynamic and reversible post-transcriptional modification and the most prevalent internal RNA modification in eukaryotic cells. YT521-B homology domain family 2 (YTHDF2) is a member of m6A "readers" and its role in human diseases remains unclear. Accumulating evidence suggests that YTHDF2 is greatly implicated in many aspects of human cancers and non-cancers through various mechanisms. YTHDF2 takes a great part in multiple biological processes, such as migration, invasion, metastasis, proliferation, apoptosis, cell cycle, cell viability, cell adhesion, differentiation and inflammation, in both human cancers and non-cancers. Additionally, YTHDF2 influences various aspects of RNA metabolism, including mRNA decay and pre-ribosomal RNA (pre-rRNA) processing. Moreover, emerging researches indicate that YTHDF2 predicts the prognosis of different cancers. Herein, we focus on concluding YTHDF2-associated mechanisms and potential biological functions in kinds of cancers and non-cancers, and its prospects as a prognostic biomarker.

Keywords: Biological function; Cancers; Non-cancers; Up and downregulation; YTHDF2; m6A; signaling pathways.

Fig. 1

The role of YTHDF2 in human cancers and non-cancers. YTHDF2 took a great part in prostate cancer, bladder cancer, hepatocellular carcinoma, cervical cancer, osteosarcoma, AML and pancreatic cancer through modulating miR-403-3p, SETD7, KLF4, SOCS2, OCT4, IL11, SERPINE2, MEK, ERK, EGFR, CDK1, WEE1, circ0001105, PER1 and ATM-CHK2-P53/CDC25C. The modulation processes were closely related with tumor cell migration, invasion, metastasis, proliferation, apoptosis, cell cycle, cell viability and inflammation. In addition, YTHDF2 played an important role in hematopoietic stem cells, pluripotent stem cells, adipogenesis, virus infection, and male and female fertility by regulating proliferation-related genes, survival-related genes, neural-specific gene, JAK1/2, SOCS3, CCNA2, CDK2, FAM134B, Tnfrsf2, ORF50 and MMPs. The regulation process were strongly related with cell self-renewal, regenerative, differentiation, proliferation, MCE, cell cycle, apoptosis and cell adhesion

Fig. 2

The structure of YTH domain in YTHDF2