The function and clinical implication of YTHDF1 in the human system development and cancer

Abstract

YTHDF1 is a well-characterized m6A reader protein that is essential for protein translation, stem cell self-renewal, and embryonic development. YTHDF1 regulates target gene expression by diverse molecular mechanisms, such as promoting protein translation or modulating the stability of mRNA. The cellular levels of YTHDF1 are precisely regulated by a complicated transcriptional, post-transcriptional, and post-translational network. Very solid evidence supports the pivotal role of YTHDF1 in embryonic development and human cancer progression. In this review, we discuss how YTHDF1 influences both the physiological and pathological biology of the central nervous, reproductive and immune systems. Therefore we focus on some relevant aspects of the regulatory role played by YTHDF1 as gene expression, complex cell networking: stem cell self-renewal, embryonic development, and human cancers progression. We propose that YTHDF1 is a promising future cancer biomarker for detection, progression, and prognosis. Targeting YTHDF1 holds therapeutic potential, as the overexpression of YTHDF1 is associated with tumor resistance to chemotherapy and immunotherapy.

METTL3-dependent m6A modification of PSEN1 mRNA regulates craniofacial development through the Wnt/β-catenin signaling pathway

“…RNA pull-down and RIP assays demonstrated that YTHDF1, but not the other readers, could bind to PSEN1 mRNA. YTHDF1 is an important m 6 A modification reader, and its primary function is to promote protein translation or regulate the stability of m 6 A-modified mRNAs [ 49 , 50 ]. Notably, YTHDF1 knockdown attenuated ameliorated pulmonary artery smooth muscle cell proliferation, phenotypic switching, and the development of pulmonary hypertension by enhancing MAGED1 translation both in vivo and in vitro [ 51 ].…”

Clinical significance of RNA methylation in hepatocellular carcinoma

“…It participates in several crucial physiological or pathological processes, such as cell proliferation, embryonic development, tumorigenesis, and neurogenesis [ 49 – 52 ]. RNA modification is a reversible process dynamically coordinated by a series of catalytically active methyltransferases, demethylases, and methylation-recognition proteins [ 53 – 55 ]. Taking the particularly well-investigated m6A methylation process as an example, adenylate methylation is performed by the methyltransferase complex.…”

YTHDF1 enhances stemness and chemoresistance in triple‐negative breast cancer cells by upregulating SIAH2

“…The m6A is catalyzed by a multicomponent protein complex including methyltransferases (METTL3, METTL14, and KIAA1429), demethylases (FTO and ALKBH5), and m6A‐binding proteins (YTHDF1‐3, YTHDC1, and YTHDC2) 8 . Studies have found that the upregulation of YTHDF1 promotes tumorigenesis and metastasis, which is related to poor prognosis of various tumors 9,10 . In addition, the upregulation of YTHDF1 promotes the stemness features and chemotherapy resistance of tumor cells 11,12 .…”

“…8 Studies have found that the upregulation of YTHDF1 promotes tumorigenesis and metastasis, which is related to poor prognosis of various tumors. 9,10 In addition, the upregulation of YTHDF1 promotes the stemness features and chemotherapy resistance of tumor cells. 11,12 However, the role of YTHDF1 in TNBC is currently unclear.…”