Unfurling the functional association between long intergenic noncoding RNAs (lincRNAs) and HPV16-related cervical cancer pathogenesis through weighted gene co-expression network analysis of differentially expressed lincRNAs and coding genes.

IF 3.3 3区 医学 Q2 ONCOLOGY
Abarna Sinha, Sahana Ghosh, Abhisikta Ghosh, Arnab Ghosh, Sonia Mathai, Jaydip Bhaumik, Asima Mukhopadhyay, Arindam Maitra, Nidhan K Biswas, Sharmila Sengupta
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引用次数: 0

Abstract

Long intergenic noncoding RNAs (lincRNAs) do not overlap annotated coding genes and are located in intergenic regions, as opposed to antisense and sense-intronic lncRNAs, located in genic regions. LincRNAs influence gene expression profiles and are thereby key to disease pathogenesis. In this study, we assessed the association between lincRNAs and HPV16-positive cervical cancer (CaCx) pathogenesis using weighted gene co-expression network analysis (WGCNA) with coding genes, comparing differentially expressed lincRNA and coding genes (DElincGs and DEcGs, respectively) in HPV16-positive patients with CaCx (n = 44) with those in HPV-negative healthy individuals (n = 34). Our analysis revealed five DElincG modules, co-expressing and correlating with DEcGs. We validated a substantial number of such module-specific correlations in the HPV16-positive cancer TCGA-CESC dataset. Four such modules, displayed significant correlations with patient traits, such as HPV16 physical status, lymph node involvement and overall survival (OS), highlighting a collaborative effect of all genes within specific modules on traits. Using the DAVID bioinformatics knowledgebase, we identified the underlying biological processes associated with these modules as cancer development and progression-associated pathways. Next, we identified the top 10 DElincGs with the highest connectivity within each functional module. Focusing on the prognostic module hub genes, downregulated CTD-2619J13.13 expression was associated with poor patient OS. This lincRNA gene interacted with 25 coding genes of its module and was associated with such biological processes as keratinization loss and keratinocyte differentiation, reflecting severe disease phenotypes. This study has translational relevance in fighting various cancers with high mortality rates in underdeveloped countries.

通过对差异表达的长基因间非编码RNA(lincRNA)和编码基因进行加权基因共表达网络分析,揭示长基因间非编码RNA(lincRNA)与HPV16相关宫颈癌发病机制之间的功能性关联。
长基因间非编码 RNA(lincRNA)与注释的编码基因不重叠,位于基因间区域,而反义和有义内切 lncRNA 则位于基因区域。LincRNA 影响基因表达谱,因此是疾病发病机制的关键。在这项研究中,我们利用加权基因共表达网络分析(WGCNA)评估了LincRNA与HPV16阳性宫颈癌(CaCx)发病机制之间的关联,比较了HPV16阳性宫颈癌患者(44人)与HPV阴性健康人(34人)中差异表达的LincRNA和编码基因(分别为DElincGs和DEcGs)。我们的分析揭示了与 DEcGs 共同表达和相关的五个 DElincG 模块。我们在 HPV16 阳性癌症 TCGA-CESC 数据集中验证了大量此类特定模块的相关性。其中四个模块与患者的特征(如 HPV16 物理状态、淋巴结受累和总生存率(OS))有明显的相关性,突显了特定模块内的所有基因对特征的协同作用。利用 DAVID 生物信息学知识库,我们将与这些模块相关的潜在生物过程确定为癌症发展和进展相关通路。接下来,我们确定了每个功能模块中连接性最高的前 10 个 DElincGs。以预后模块枢纽基因为重点,CTD-2619J13.13表达下调与患者不良的OS有关。该lincRNA基因与其模块中的25个编码基因相互作用,与角质化丧失和角质细胞分化等生物过程相关,反映了严重的疾病表型。这项研究对不发达国家抗击高死亡率的各种癌症具有转化意义。
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来源期刊
Carcinogenesis
Carcinogenesis 医学-肿瘤学
CiteScore
9.20
自引率
2.10%
发文量
95
审稿时长
1 months
期刊介绍: Carcinogenesis: Integrative Cancer Research is a multi-disciplinary journal that brings together all the varied aspects of research that will ultimately lead to the prevention of cancer in man. The journal publishes papers that warrant prompt publication in the areas of Biology, Genetics and Epigenetics (including the processes of promotion, progression, signal transduction, apoptosis, genomic instability, growth factors, cell and molecular biology, mutation, DNA repair, genetics, etc.), Cancer Biomarkers and Molecular Epidemiology (including genetic predisposition to cancer, and epidemiology), Inflammation, Microenvironment and Prevention (including molecular dosimetry, chemoprevention, nutrition and cancer, etc.), and Carcinogenesis (including oncogenes and tumor suppressor genes in carcinogenesis, therapy resistance of solid tumors, cancer mouse models, apoptosis and senescence, novel therapeutic targets and cancer drugs).
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