The potential role of m6A reader YTHDF1 as diagnostic biomarker and the signaling pathways in tumorigenesis and metastasis in pan-cancer

Abstract

m6A is an important RNA methylation in progression of various human cancers. As the m6A reader protein, YTHDF1 is reported to accelerate m6A-modified mRNAs translation in cytoplasm. It is highly expressed in various human cancers and contributes to the progression and metastasis of cancers. YTHDF1 was closely associated with poor prognosis and also used as a molecular marker for clinical diagnosis or therapy in human cancers. It has been reported to promote chemoresistance to Adriamycin, Cisplatin and Olaparib by increasing mRNA stability of its target molecule. Moreover, it contributes to CSC-like characteristic of tumor cells and inducing the antitumor immune microenvironment. Here, we reviewed the clinical diagnostic and prognostic values of YTHDF1, as well as the molecular mechanisms of YTHDF1 in progression and metastasis of human cancers.

Fig. 1. m6A methylation modification.

A The methylation modification process of m6A is reversible and requires the participation of methyltransferases, demethylases and methylation reading proteins. Methylase including METTL3/13, WTAP, RBM15 etc. The main role is to catalyze the m6A modification of adenylate on mRNA. Demethylases, including FTO and ALKHB5, are used to demethylate bases that have undergone m6A modification. The main function of reader proteins including YTHDF1/2/3, YTHDC1/2 etc. is to recognize bases with m6A modification, thereby activating downstream regulatory pathways, such as RNA degradation, miRNA processing, etc. B The molecular biological function regulated by m6A methylation modification, including alternative splicing, structure switching, stability, export, microRNA maturation, X chromosome inactivation, translation and mRNA decay etc.

Fig. 2. The diagnostic value of YTHDF1 in human cancers.

A YTHDF1 was potentially used as the biomarker for early diagnosis with high specificity and sensitivity in various human cancers. LUAD, READ, PAAD, THYM, STAD, ESAD, ESCA, BRCA, COAD, GBMLGG, LIHC, and LUSC. B DNA copy number amplification of YTHDF1 in 10712 samples from 32 studies with various cancers based on cBioPortal database.

Fig. 3. The related signaling pathway on YTHDF1 in tumorigenesis and metastasis of virous cancers.

A The key regulatory non-coding RNA(lncRNAs, miRNAs) and proteins were shown which were involved in YTHDF1 related signaling pathways. B The targeted proteins regulated by YTHDF1 in tumorigenesis and metastasis.

Fig. 4

The key proteins involved in CSCs-like properties regulated by YTHDF1.