Abstract
YTH domain containing 2 (YTHDC2) is the largest N6‐Methyladenosine (m6A) binding protein of the YTH protein family and the only member containing ATP‐dependent RNA helicase activity. For further analysing its biological role in epigenetic modification, we comprehensively explored YTHDC2 from gene expression, genetic alteration, protein‐protein interaction (PPI) network, immune infiltration, diagnostic value and prognostic value in pan‐cancer, using a series of databases and bioinformatic tools. We found that YTHDC2 with Missense mutation could cause a different prognosis in uterine corpus endometrial carcinoma (UCEC), and its different methylation level could lead to a totally various prognosis in adrenocortical carcinoma (ACC), cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), lung squamous cell carcinoma (LUSC) and UCEC. The main molecular mechanisms of YTHDC2 focused on catalytic activity, helicase activity, snRNA binding, spliceosome and mRNA surveillance. Additionally, YTHDC2 was notably correlated with tumour immune infiltration. Moreover, YTHDC2 had a high diagnostic value for seven cancer types and a prognostic value for brain lower grade glioma (LGG), rectum adenocarcinoma (READ) and skin cutaneous melanoma (SKCM). Collectively, YTHDC2 plays a significant role in epigenetic modification and immune infiltration and maybe a potential biomarker for diagnosis and prognosis in certain cancers.
Highlights
In recent years, as the most abundant mRNA modification in eukaryotic cells,[1] m6A RNA modification is widely recognized as an essential epigenetic modification in many biological processes by the dynamic adjustment of gene expression and receives considerable attention
The results showed that YTH domain containing 2 (YTHDC2) expression was significantly positively correlated with the infiltration levels of CD8+ T cell, CD4+ T cell, neutrophil, myeloid dendritic cell, macrophage and B cell in five types of cancer, containing colon adenocarcinoma (COAD), kidney renal clear cell carcinoma (KIRC), liver hepatocellular carcinoma (LIHC), lung adenocarcinoma (LUAD) and pancreatic adenocarcinoma (PAAD)
Recent studies have reported that YTHDC2 plays a key role in meiosis and spermatogenesis.10-13 Existing research has recognized the critical part played by YTHDC2 in the initiation and progression of diseases including cancers
Summary
As the most abundant mRNA modification in eukaryotic cells,[1] m6A RNA modification is widely recognized as an essential epigenetic modification in many biological processes by the dynamic adjustment of gene expression and receives considerable attention. It is well established that m6A modification is crucial for various pathological processes, including cancer initiation and progression.2-6 the dedicated methyltransferases (writers) and demethylases (erasers) regulate the reversibility of m6A modification, which does not alter the matching and coding of bases, m6A binding proteins (readers) are vital to the fate of mRNAs through specific recognizing m6A and binding function during various bioprocesses, such as RNA splicing, export, translation and decay,[1] widely affecting gene expression at different levels. YTHDC2 prefers to bind to the conserved m6A-modified motifs and executives the function of m6A reader by enhancing the translation efficiency and decreasing the mRNA abundance.10-13 Previous studies have shown that YTHDC2 has a crucial effect on cancer metastasis through increased translation efficiency of HIF-1α in colon cancer patients[14] and contributes significantly in the proliferation of hepatocellular carcinoma cells.[15] YTHDC2 expression has been identified to be associated with prognosis, apoptosis activation and ubiquitin-mediated proteolysis in Head and Neck squamous cell carcinoma (HNSCC).[16]. The pan-cancer analysis may contribute to uncovering the distinct roles of YTHDC2 in the varying cancer promotion or suppression and provide evidence for more directional clinical and experimental research in individual cancers
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
