Small nucleolar RNAs (snoRNAs), a distinct class of noncoding RNAs, encompass highly diverse structures and have a range of 60 to 300 nucleotides in length. About 90% of human snoRNAs are intronic and embedded within introns of their host gene transcripts. Most snoRNAs enriched in specific tissue correlate in abundance with their parental host genes. Advancements in high-throughput sequencing have facilitated the discovery of dysregulated snoRNA expression in numerous human malignancies including head and neck squamous cell carcinoma (HNSCC). Hundreds of differentially expressed snoRNAs have been identified in HNSCC tissues. Among 1,524 snoRNA genes in a 567 HNSCC cohort, 113 snoRNAs were found to be survival related. As for snoRNA’s roles in HNSCC, based on the available evidence, dysregulated snoRNAs are closely associated with the carcinogenesis and development of HNSCC. Upregulated snoRNAs have been shown to augment the expression of other oncogenes or activate the Wnt/β-catenin signaling pathway, thereby promoting tumor cell viability, glycolysis, migration, and the epithelial-mesenchymal transition while inhibiting apoptosis in vitro. In vivo animal studies have further elucidated the functional roles of snoRNAs. Knockdown of host genes of these snoRNAs suppressed the Wnt/β-catenin signaling pathway and restrained tumor proliferation and aggressiveness in mice. The putative mechanisms underlying these observations are associated with the biological functions of snoRNAs, primarily involving microRNA-like functions through the generation of microRNA-like fragments and regulation of alternative splicing to yield diverse transcripts. While most of the snoRNAs are upregulated in HNSCC, 4 downregulated snoRNAs have been identified and annotated. SNORA36B (implicated in the regulation of DNA templates) and U3 (chr17, influencing cell proliferation) may serve as protective factors associated with prolonged overall survival. This review describes the viable structures of snoRNAs, endeavors to refine snoRNA sequencing technology, and summarizes snoRNAs’ expression profile as well as their role in HNSCC progression for potential diagnostic and therapeutic strategies for HNSCC management.

中文翻译：

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头颈部鳞状细胞癌中的小核仁 RNA


小核仁 RNA （snoRNA） 是一类独特的非编码 RNA，包含高度多样化的结构，长度范围为 60 至 300 个核苷酸。大约 90% 的人类 snoRNA 是内含子的，并嵌入其宿主基因转录本的内含子中。大多数在特定组织中富集的 snoRNA 与其亲本宿主基因的丰度相关。高通量测序的进步促进了在包括头颈部鳞状细胞癌 （HNSCC） 在内的许多人类恶性肿瘤中发现 snoRNA 表达失调。已在 HNSCC 组织中鉴定出数百种差异表达的 snoRNA。在 567 个 HNSCC 队列的 1,524 个 snoRNA 基因中，发现 113 个 snoRNA 与生存相关。至于 snoRNA 在 HNSCC 中的作用，根据现有证据，失调的 snoRNAs 与 HNSCC 的致癌发生和发展密切相关。上调的 snoRNA 已被证明可以增加其他癌基因的表达或激活 Wnt/β-catenin 信号通路，从而促进肿瘤细胞活力、糖酵解、迁移和上皮-间质转化，同时抑制体外细胞凋亡。体内动物研究进一步阐明了 snoRNA 的功能作用。敲低这些 snoRNAs 的宿主基因抑制了 Wnt/β-catenin 信号通路，抑制了小鼠的肿瘤增殖和侵袭性。这些观察结果背后的推定机制与 snoRNA 的生物学功能有关，主要涉及通过产生 microRNA 样片段和调节选择性剪接以产生不同转录本的 microRNA 样功能。虽然大多数 snoRNAs 在 HNSCC 中上调，但已鉴定并注释了 4 种下调的 snoRNA。 SNORA36B （与 DNA 模板的调节有关） 和 U3 （chr17，影响细胞增殖） 可作为与延长总生存期相关的保护因子。本文综述了 snoRNAs 的可行结构，努力改进 snoRNA 测序技术，并总结了 snoRNAs 的表达谱及其在 HNSCC 进展中的作用，为 HNSCC 管理的潜在诊断和治疗策略提供了指导。