Decoding dysregulated genes, molecular pathways and microRNAs involved in cervical cancer

IF 3.2 4区 医学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Journal of Gene Medicine Pub Date : 2024-07-01 DOI:10.1002/jgm.3713
Manoj Khokhar, Purnima Kartha, Sana Hassan, Rajan Kumar Pandey
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Abstract

Background

The present study aimed to identify dysregulated genes, molecular pathways, and regulatory mechanisms in human papillomavirus (HPV)-associated cervical cancers. We have investigated the disease-associated genes along with the Gene Ontology, survival prognosis, transcription factors and the microRNA (miRNA) that are involved in cervical carcinogenesis, enabling a deeper comprehension of cervical cancer linked to HPV.

Methods

We used 10 publicly accessible Gene Expression Omnibus (GEO) datasets to examine the patterns of gene expression in cervical cancer. Differentially expressed genes (DEGs), which showed a clear distinction between cervical cancer and healthy tissue samples, were analyzed using the GEO2R tool. Additional bioinformatic techniques were used to carry out pathway analysis and functional enrichment, as well as to analyze the connection between altered gene expression and HPV infection.

Results

In total, 48 DEGs were identified to be differentially expressed in cervical cancer tissues in comparison to healthy tissues. Among DEGs, CCND1, CCNA2 and SPP1 were the key dysregulated genes involved in HPV-associated cervical cancer. The five common miRNAs that were identified against these genes are miR-7-5p, miR-16-5p, miR-124-3p, miR-10b-5p and miR-27a-3p. The hub-DEGs targeted by miRNA hsa-miR-27a-3p are controlled by the common transcription factor SP1.

Conclusions

The present study has identified DEGs involved in HPV-associated cervical cancer progression and the various molecular pathways and transcription factors regulating them. These findings have led to a better understanding of cervical cancer resulting in the development and identification of possible therapeutic and intervention targets, respectively.

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解码宫颈癌相关的失调基因、分子通路和 microRNA。
研究背景本研究旨在确定人乳头瘤病毒(HPV)相关宫颈癌中的失调基因、分子通路和调控机制。我们对疾病相关基因以及基因本体、生存预后、转录因子和参与宫颈癌发生的微RNA(miRNA)进行了研究,从而更深入地了解与HPV相关的宫颈癌:我们使用了 10 个可公开访问的基因表达总库(GEO)数据集来研究宫颈癌的基因表达模式。我们使用 GEO2R 工具分析了宫颈癌与健康组织样本之间有明显区别的差异表达基因(DEGs)。此外,还利用生物信息学技术进行了通路分析和功能富集,并分析了基因表达改变与 HPV 感染之间的联系:结果:与健康组织相比,宫颈癌组织中共有 48 个 DEGs 存在差异表达。在 DEGs 中,CCND1、CCNA2 和 SPP1 是 HPV 相关宫颈癌的关键失调基因。针对这些基因的五种常见 miRNA 包括 miR-7-5p、miR-16-5p、miR-124-3p、miR-10b-5p 和 miR-27a-3p。miRNA hsa-miR-27a-3p 靶向的枢纽-DEGs 受共同转录因子 SP1 的控制:本研究发现了参与 HPV 相关宫颈癌进展的 DEGs,以及调控这些 DEGs 的各种分子通路和转录因子。这些发现使人们对宫颈癌有了更深入的了解,从而分别开发和确定了可能的治疗和干预靶点。
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来源期刊
Journal of Gene Medicine
Journal of Gene Medicine 医学-生物工程与应用微生物
CiteScore
6.40
自引率
0.00%
发文量
80
审稿时长
6-12 weeks
期刊介绍: The aims and scope of The Journal of Gene Medicine include cutting-edge science of gene transfer and its applications in gene and cell therapy, genome editing with precision nucleases, epigenetic modifications of host genome by small molecules, siRNA, microRNA and other noncoding RNAs as therapeutic gene-modulating agents or targets, biomarkers for precision medicine, and gene-based prognostic/diagnostic studies. Key areas of interest are the design of novel synthetic and viral vectors, novel therapeutic nucleic acids such as mRNA, modified microRNAs and siRNAs, antagomirs, aptamers, antisense and exon-skipping agents, refined genome editing tools using nucleic acid /protein combinations, physically or biologically targeted delivery and gene modulation, ex vivo or in vivo pharmacological studies including animal models, and human clinical trials. Papers presenting research into the mechanisms underlying transfer and action of gene medicines, the application of the new technologies for stem cell modification or nucleic acid based vaccines, the identification of new genetic or epigenetic variations as biomarkers to direct precision medicine, and the preclinical/clinical development of gene/expression signatures indicative of diagnosis or predictive of prognosis are also encouraged.
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