hsa_circ_0003098和hsa_circ_0013958在肾细胞癌病理生理中的潜在作用

IF 0.9 Q4 GENETICS & HEREDITY

Gene Reports Pub Date : 2025-06-11 DOI:10.1016/j.genrep.2025.102275

Hosein Mansoori , Zahra Firoozi , Elham Mohammadisoleimani , Farshad Dehghani , Masoomeh Rahpeima , Mahsa Saffar , Mohammad Mehdi Naghizadeh , Ali Ariafar , Shahryar Zeighami , Yaser Mansoori

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引用次数: 0

摘要

肾细胞癌（RCC）是肾癌的主要形式，某些亚型预后相对较差。环状RNA （circRNAs）最近成为内源性RNA （ceRNA）竞争网络背景下早期诊断更恶性亚型的有希望的工具。材料和方法这是一项实验和计算机研究hsa_circ_0003098和hsa_circ_0013958在RCC肿瘤和健康组织中的表达及其与相关mirna和mrna的相互作用。使用qRT-PCR评估表达，使用CircInteractome、miRTargetlink2、TargetScan、mirwalk和STRING数据库构建ceRNA网络。生存分析采用GEPIA，网络分析采用Cytoscape。采用受试者工作特征（ROC）曲线分析评价hsa_circ_0003098和hsa_circ_0013958的临床和诊断价值。结果hsa_circ_0003098和hsa_circ_0013958在肿瘤组织中的表达水平均显著低于正常组织(p值=0.013,<；0.001)。有趣的是，hsa_circ_0013958的表达与肾脏疾病和肿瘤类型之间存在显著关联。ceRNA网络的计算机分析鉴定了对RCC至关重要的mrna和mirna。与每个circRNA相关的枢纽基因的生存分析揭示了几个显著影响患者生存的基因。hsa_circ_0003098和hsa_circ_0013958可作为RCC的诊断标志物。结论我们的研究表明hsa_circ_0003098和hsa_circ_0013958在RCC肿瘤中显著下调。这种miRNA/mRNA网络的失调影响了重要的致癌过程，如粘附、迁移、信号传导和细胞周期，这反过来又为RCC的分子机制提供了见解。

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Potential roles of hsa_circ_0003098 and hsa_circ_0013958 in pathophysiology of renal cell carcinoma

Background

Renal cell carcinoma (RCC) is the predominant form of kidney cancer with certain subtypes carrying a relatively poor prognosis. Circular RNAs (circRNAs) have recently emerged as promising tools for early diagnosis of the more malignant subtypes in the context of competing endogenous RNA (ceRNA) networks.

Materials and methods

This is an experimental and in-silico study of the expression of hsa_circ_0003098 and hsa_circ_0013958 and their interaction with associated miRNAs and mRNAs in the context of tumor versus healthy tissues in RCC. The expression was assessed using qRT-PCR and ceRNA network was constructed using CircInteractome, miRTargetlink2, TargetScan, miRWallk, and STRING databases. GEPIA was employed for survival analysis and Cytoscape was used for network analysis. Receiver Operating Characteristic (ROC) curve analysis was used to evaluate the clinical and diagnostic value of hsa_circ_0003098 and hsa_circ_0013958.

Results

Both hsa_circ_0003098 and hsa_circ_0013958 were expressed at significantly lower levels in tumor tissues compared with normal tissues (P-value =0.013, < 0.001). Interestingly, there was a significant association between the expression of hsa_circ_0013958 and kidney disease and tumor type. In silico analysis of the ceRNA network identified mRNAs and miRNAs crucial for RCC. Survival analysis of hub genes linked to each circRNA revealed several genes significantly impacting patient survival. Besides, hsa_circ_0003098 and hsa_circ_0013958 could act as diagnostic markers in RCC.

Conclusion

Our research showed that hsa_circ_0003098 and hsa_circ_0013958 were significantly downregulated in RCC tumors. This dysregulation of their miRNA/mRNA network affected important carcinogenic processes such as adhesion, migration, signaling, and cell cycle, which in turn provided insights into the molecular mechanisms of RCC.

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来源期刊

Gene Reports Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

3.30

自引率

7.70%

发文量

246

审稿时长

49 days

期刊介绍： Gene Reports publishes papers that focus on the regulation, expression, function and evolution of genes in all biological contexts, including all prokaryotic and eukaryotic organisms, as well as viruses. Gene Reports strives to be a very diverse journal and topics in all fields will be considered for publication. Although not limited to the following, some general topics include: DNA Organization, Replication & Evolution -Focus on genomic DNA (chromosomal organization, comparative genomics, DNA replication, DNA repair, mobile DNA, mitochondrial DNA, chloroplast DNA). Expression & Function - Focus on functional RNAs (microRNAs, tRNAs, rRNAs, mRNA splicing, alternative polyadenylation) Regulation - Focus on processes that mediate gene-read out (epigenetics, chromatin, histone code, transcription, translation, protein degradation). Cell Signaling - Focus on mechanisms that control information flow into the nucleus to control gene expression (kinase and phosphatase pathways controlled by extra-cellular ligands, Wnt, Notch, TGFbeta/BMPs, FGFs, IGFs etc.) Profiling of gene expression and genetic variation - Focus on high throughput approaches (e.g., DeepSeq, ChIP-Seq, Affymetrix microarrays, proteomics) that define gene regulatory circuitry, molecular pathways and protein/protein networks. Genetics - Focus on development in model organisms (e.g., mouse, frog, fruit fly, worm), human genetic variation, population genetics, as well as agricultural and veterinary genetics. Molecular Pathology & Regenerative Medicine - Focus on the deregulation of molecular processes in human diseases and mechanisms supporting regeneration of tissues through pluripotent or multipotent stem cells.