m 6 A reader YTHDF2 orchestrates CD8 + T cell infiltration to promote pancreatic cancer progression and predicts clinical outcome.

Autor: Tan Z; Department of Hepatobiliary Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China; Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Shanghai Pancreatic Cancer Institute, Shanghai 200032, China; Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China., Hei F; Department of Hepatobiliary Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China., Ma K; Department of Hepatobiliary Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China., Lv Z; Department of Hepatobiliary Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China., Zhang H; Department of Hepatobiliary Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China., Sun N; Department of Hepatobiliary Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China., Guo W; Department of Hepatobiliary Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China. Electronic address: guoeweid123@163.com., Song M; Department of Hepatobiliary Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China. Electronic address: songmengqi@qdu.edu.cn.
Jazyk: angličtina
Zdroj: International immunopharmacology [Int Immunopharmacol] 2024 Dec 05; Vol. 142 (Pt B), pp. 113079. Date of Electronic Publication: 2024 Sep 16.
DOI: 10.1016/j.intimp.2024.113079
Abstrakt: Pancreatic cancer has emerged as one of the most lethal malignancies, characterized by rising morbidity and mortality rates. Research has demonstrated that N6-methyladenosine (m 6 A) modification of RNA significantly influences RNA metabolism, and dysregulation of m 6 A is implicated in various human diseases. A clearer picture of how the divergent m 6 A methylation patterns affect immunological microenvironment in pancreatic cancer is still unknown. Based on an analysis of RNA-sequencing (RNA-seq) data from the TCGA, GEO, and GTEx databases, we predicted and validated the expression of YTHDF2. Apoptosis and cell cycle analyses of YTHDF2 were conducted using flow cytometry, and a subcutaneous transplantation tumor model was established in BALB/c nude mice. The immune infiltration status and Weighted Gene Co-expression Network Analysis (WGCNA) were employed to evaluate cellular immunity and identify downstream target genes associated with the CD8 + T cell module. Additionally, machine learning-based integrative approaches were utilized to generate a predictive signature. The Western blot technique was employed to quantify YTHDF2 expression levels in PDAC cell lines and tissues. WGCNA and PPI unveiled TFG as the core gene regulation network conducting the function of the CD8 + T cell. Quantitative reverse transcription PCR (qRT-PCR) assays were conducted to confirm the reduction in TFG expression subsequent to YTHDF2 knockdown. Integrative analyses using large-scale genomic data sets were conducted to reveal that YTHDF2 could affect pancreatic cancer cell apoptosis and the cell cycle, promote malignant biologic processes, and gene regulation in immune cells. YTHDF2 potentially modulates crucial molecular subgroups of immune checkpoint molecules in CD8 + T cells, thereby enhancing tumor immunogenicity and promoting anti-tumor immune responses.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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