Gu Yuxi, Tang Shouyi, Wang Zhen, Cai Luyao, Shen Yingqiang, Zhou Yu
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, 610041, Chengdu, China.
J Dent Sci. 2022 Apr;17(2):666-676. doi: 10.1016/j.jds.2021.08.016. Epub 2021 Sep 6.
BACKGROUND/PURPOSE: Oral squamous cell carcinoma (OSCC) is one of the most common types of head and neck squamous cell carcinoma. Accurate biomarkers are needed for early diagnosis and prognosis of OSCC. MicroRNAs (miRNAs) have shown great values in different types of cancers including OSCC. However, most of the miRNAs involved in the development of OSCC remain uncovered. This study aimed to identify hub miRNAs and mRNAs in OSCC.
We explored the roles of key miRNAs, target genes and their relationships in OSCC using an integrated bioinformatics approach. Initially, Two OSCC microarray datasets from the Gene Expression Omnibus database were obtained to analyze miRNA expression. MiRNA-targeted mRNAs were acquired, and gene ontology/kyoto encyclopedia of genes and genomes analyses were performed. Thereafter, we constructed a protein-protein interaction (PPI) network to identify hub genes and a miRNA-mRNA interaction network was used to identify key miRNAs. Furthermore, differential gene expression and Kaplan-Meier Plotter survival analysis was performed to evaluate their potential clinical application values.
Four upregulated, two downregulated miRNAs and 608 target genes of the differentially expressed miRNAs were identified. The PPI and miRNA-mRNA interaction networks highlighted 10 hub genes and two key miRNAs, and pathway analyses showed their correlative involvement in tumorigenesis-related processes. Of these miRNAs and genes, miR-125b, β-actin, vinculin and histone deacetylase 1 were correlated with overall survival (P < 0.05).
These findings indicate that miR-21 and miR-125b, associated with the 10 hub genes, jointly participate in OSCC tumorigenesis, offering insight into the molecular mechanisms underlying OSCC as potential targets for early diagnosis, treatment and prognosis.
背景/目的:口腔鳞状细胞癌(OSCC)是头颈部鳞状细胞癌最常见的类型之一。OSCC的早期诊断和预后需要准确的生物标志物。微小RNA(miRNA)在包括OSCC在内的不同类型癌症中已显示出巨大价值。然而,大多数参与OSCC发生发展的miRNA仍未被发现。本研究旨在鉴定OSCC中的关键miRNA和mRNA。
我们采用综合生物信息学方法探讨关键miRNA、靶基因在OSCC中的作用及其相互关系。首先,从基因表达综合数据库获取两个OSCC微阵列数据集以分析miRNA表达。获取miRNA靶向的mRNA,并进行基因本体论/京都基因与基因组百科全书分析。此后,我们构建了蛋白质-蛋白质相互作用(PPI)网络以鉴定枢纽基因,并使用miRNA-mRNA相互作用网络鉴定关键miRNA。此外,进行差异基因表达和Kaplan-Meier Plotter生存分析以评估它们潜在的临床应用价值。
鉴定出4个上调、2个下调的miRNA以及差异表达miRNA的608个靶基因。PPI和miRNA-mRNA相互作用网络突出显示了10个枢纽基因和2个关键miRNA,通路分析表明它们相关参与肿瘤发生相关过程。在这些miRNA和基因中,miR-125b、β-肌动蛋白、纽蛋白和组蛋白脱乙酰基酶1与总生存期相关(P<0.05)。
这些发现表明,与10个枢纽基因相关的miR-21和miR-125b共同参与OSCC的肿瘤发生,为深入了解OSCC潜在的早期诊断、治疗和预后分子机制提供了线索。