■头颈部鳞状细胞癌(HNSCC)是一种恶性肿瘤,其特征是发病率和复发率高。5-甲基胞嘧啶(m5C)RNA修饰是影响癌症进展的常见改变;然而,m5C如何在HNSCC的肿瘤微环境中运作还有待阐明。
■我们对来自中期和晚期HNSCC的3对癌症和癌旁组织进行了纳米孔测序,获得132个上调的基因(转录上调,m5C升高)和129个下调基因(转录下调,m5C减少)。随后进行了基因本体论(GO)和京都基因和基因组百科全书(KEGG)富集分析;构建了差异基因相互作用网络(PPI),揭示网络中每个基因与其他基因的相互作用。对PPI内的基因进行共表达分析,揭示他们的表达和监管关系。通过GSVA分析,确定了不同状态下相关途径的变化。此外,lncRNA中m5C的筛选结果,其次是靶基因预测。
■来自3对中晚期HNSCC癌和癌旁组织的测序结果表明,RPS27A,RPL8和lncRNAs,包括分化拮抗非蛋白编码RNA(DANCR),DCST1反义RNA1(CCDC144NL-AS1),增长逮捕特定转录本5(GAS5),核旁斑装配转录本1(NEAT1),和小核仁RNA宿主基因3(SNHG3),等。,根据m5C规定,与周围的基因有密切的联系。差异m5C修饰基因主要参与核糖体蛋白合成,氧化应激反应,代谢重编程,豁免权,和其他生命过程;线粒体蛋白导入和光动力疗法诱导的未折叠蛋白反应等途径在肿瘤中上调,而路径,包括经典的P53,都被压制了。对m5C调节的长链非编码RNA(lncRNA)的分析也揭示了与RPS27A和RPL8的紧密关联。
■我们的研究确定了HNSCC中涉及m5C的关键因素和信号通路。研究结果表明,核糖体相关基因可能调节核糖体蛋白的合成,氧化应激反应,代谢重编程,通过缺氧和铁凋亡等方式通过m5CRNA修饰进行免疫反应,从而在HNSCC的发生和发展中起关键作用。因此,应注意核糖体在HNSCC中的作用。这些发现可能有助于临床中,晚期HNSCC患者的精确和个性化治疗。
UNASSIGNED: Head and Neck Squamous Cell Carcinoma (HNSCC) is a malignancy characterized by a high incidence and recurrence rate. 5-methylcytosine (m5C) RNA modification is a common alteration affecting cancer progression; however, how m5C operates within the tumor microenvironment of HNSCC remains to be elucidated.
UNASSIGNED: We conducted Nanopore sequencing on 3 pairs of cancer and paracancerous tissues from mid- and late-stage HNSCC, obtaining 132 upregulated genes (transcriptomically upregulated, m5C elevated) and 129 downregulated genes (transcriptomically downregulated, m5C reduced). Subsequent Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed; a differential gene interaction network (PPI) was constructed, revealing the interactions of each gene with others in the network. Co-expression analysis was performed on the genes within the PPI, unveiling their expression and regulatory relationships. Through GSVA analysis, variations in related pathways under different states were identified. Furthermore, results of m5C in lncRNA were screened, followed by target gene prediction.
UNASSIGNED: Sequencing results from the 3 pairs of mid- and late-stage HNSCC cancer and paracancerous tissues demonstrated that RPS27A, RPL8, and the lncRNAs including differentiation antagonizing nonprotein coding RNA (DANCR), DCST1 antisense RNA 1 (CCDC144NL-AS1), Growth Arrest-Specific Transcript 5 (GAS5), Nuclear Paraspeckle Assembly Transcript 1 (NEAT1), and Small Nucleolar RNA Host Gene 3 (SNHG3), etc., under m5Cregulation, have close connections with surrounding genes. The differentially m5Cmodified genes are primarily involved in ribosomal protein synthesis, oxidative stress response, metabolic reprogramming, immunity, and other life processes; pathways like mitochondrial protein import and photodynamic therapy induced unfolded protein response are upregulated in the tumor, while pathways, including the classic P53, are suppressed. Analysis on m5C-regulated long non-coding RNAs (lncRNAs) revealed tight associations with RPS27A and RPL8 as well.
UNASSIGNED: Our study identifies the key factors and signaling pathways involving m5C in HNSCC. The findings suggest that ribosome-related genes might regulate ribosomal protein synthesis, oxidative stress response, metabolic reprogramming, and immune response through m5C RNA modification by means like hypoxia and ferroptosis, thereby playing a pivotal role in the onset and progression of HNSCC. Hence, attention should be paid to the role of ribosomes in HNSCC. These findings may facilitate the precision and individualized treatment of patients with mid- and late-stage HNSCC in clinical settings.