The Role of Protein Methylation in Squamous Cell Carcinoma of the Head and Neck

蛋白质甲基化在头颈鳞状细胞癌中的作用

• 批准号: 10262491
• 负责人: Vassiliki Saloura
• 金额: $ 68.41万
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10262491
• 关键词: ATAC-seq; Affect; Annual Reports; Antisense Oligonucleotides; CD8-Positive T-Lymphocytes; Cells; ChIP-seq; Chromatin; Chromatin Remodeling Factor; Clinical Trials; Disease; Enhancers; Family; Genes; Goals; Growth; HPV-negative head and neck cancer; Head and Neck Neoplasms; Head and Neck Squamous Cell Carcinoma; Histone-Lysine N-Methyltransferase; Histones; Human; Immune; Lysine; Metastatic/Recurrent; Methylation; Mus; Mutate; Oncogenic; Patients; Physical condensation; Protein Methylation; Protein Methyltransferases; Public Health; Recurrence; Research; Role; SMYD3 gene; The Cancer Genome Atlas; Translating; chemokine; epigenome; experimental study; genome-wide; head and neck cancer patient; immunoregulation; inhibitor/antagonist; mouse model; novel therapeutics; overexpression; transcriptome sequencing; tumor

Squamous cell carcinoma of the head and neck (SCCHN) is a significant public health concern affecting over 50,000 patients annually in the US. Recurrence rates in HPV-negative SCCHN are approximately 50%, while the median overall survival for patients with recurrent/metastatic disease is approximately 1 year, thus novel therapies are urgently needed. Protein lysine methyltransferases (PKMTs) are a class of histone modifiers that are mostly known to regulate the histone epigenome through methylation of specific histone lysine residues. With the advent of the Cancer Genome Atlas (TCGA), PMTs were found to be mutated, amplified or overexpressed in SCCHN. The role of SMYD3 in SCCHN: In this project, we will assess the immunomodulatory and oncogenic functions of SMYD3 in SCCHN. To this purpose, we will be conducting CHIP-seq, ATAC-seq and RNA-seq to identify direct downstream targets of SMYD3, assess if it affects chromatin condensation and the enhancer activation status in SCCHN cells, as well as mouse experiments to evaluate the growth and tumor immunomodulatory effects of SMYD3.

头部和颈部的鳞状细胞癌（SCCHN）是一个重大的公共卫生问题，每年在美国影响50,000多名患者。 HPV阴性SCCHN的复发率约为50％，而复发/转移性疾病患者的总体存活率大约为1年，因此紧急需要新的疗法。蛋白质赖氨酸甲基转移酶（PKMTS）是一类组蛋白修饰剂，大多数人通过特异性组蛋白赖氨酸残基的甲基化来调节组蛋白表观遗传组。随着癌症基因组地图集（​​TCGA）的出现，发现PMT在SCCHN中被突变，扩增或过表达。 SMYD3在SCCHN中的作用：在这个项目中，我们将评估SMYD3在SCCHN中的免疫调节和致癌功能。为此，我们将进行CHIP-SEQ，ATAC-SEQ和RNA-SEQ，以识别SMYD3的直接下游靶标，评估它是否影响SCCHN细胞中的染色质凝结和增强子激活状态，以及小鼠实验以评估SMYD3的生长和TUMOR免疫调节效应。