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BRCA1/2(±)卵巢癌患者外周血样本中miR-3135b和miR-1273g-3p的异常表达。

Aberrant miR-3135b and miR-1273g-3p expression in the peripheral blood samples of BRCA1/2 (±) ovarian cancer patients.

作者信息

Tuncer Seref Bugra, Celik Betul, Kılıc Erciyas Seda, Sukruoglu Erdogan Ozge, Pasin Ozge, Avsar Mukaddes, Kurt Gultaslar Busra, Adamnejad Ghafour Arash, Uyaroglu Gamze, Akdeniz Odemis Demet, Yazıcı Hulya

机构信息

Department of Cancer Genetics, Oncology Institute, Istanbul University, Istanbul, Türkiye.

Molecular Biology Department, Erzincan Binali Yıldırım University, Erzincan, Türkiye.

出版信息

Heliyon. 2023 Dec 20;10(1):e23876. doi: 10.1016/j.heliyon.2023.e23876. eCollection 2024 Jan 15.

Abstract

Ovarian cancer (OC) ranks as the eighth most prevalent malignancy among women globally. The short non-coding RNA molecules, microRNAs (miRNAs) target multiple mRNAs and regulate the gene expression. Here in this study, we aimed to validate miR-3135b and miR-1273g-3p as novel biomarkers for prognostic and diagnostic factor OC. After RNA isolation, we analyzed the miR-3135b and miR-1273g-3p expression in peripheral blood samples derived from 150 OC patients. Subsequently, we compared their expression levels with 100 healthy controls. The differences of miR-3135b and miR-1273g-3p expression were detected using the Quantitative Real Time-PCR (qRT-PCR) technique following miRNA-specific cDNA synthesis pursing miRNA separation. The miR-3135b and miR-1273g-3p were higher in OC patients who tested positive for BRCA1/2 compared to BRCA-negative patients, and healthy cases. The level of miR-3135b demonstrated a roughly 4.82-fold increase in OC patients in comparison to the healthy cases, while miR-1273g-3p expression exhibited a roughly 6.77-fold increase. The receiver operating characteristic (ROC) analysis has demonstrated the potential of miR-3135b and miR-1273g-3p as markers for distinguishing between OC patients and healthy controls. The higher expressions of miR-3135b and miR-1273g-3p could be associated with OC development. Moreover, miR-3135b may have a diagnostic potential and miR-1273g-3p may have both diagnostic and prognostic potential in OC cell differentiation. The string analysis has revealed an association between miR-1273g-3p and the gene, suggesting a potential link to tumor formation through the proteasomal degradation of the tumor suppressor gene. Additionally, the analysis indicates an association of miR-1273g-3p with , a gene involved in checkpoint-mediated cell cycle arrest. String analysis also indicates that miR-3135b is associated with the gene, causing activation of the oncogenesis cascade. In conclusion, miR-1273g-3p, and miR-3135b exhibit significant potential as diagnostic markers. However, further research is needed to comprehensively investigate these miRNAs diagnostic and predictive characteristics in a larger cohort.

摘要

卵巢癌(OC)是全球女性中第八大最常见的恶性肿瘤。短链非编码RNA分子,即微小RNA(miRNA)可靶向多个mRNA并调节基因表达。在本研究中,我们旨在验证miR - 3135b和miR - 1273g - 3p作为卵巢癌预后和诊断因素的新型生物标志物。RNA分离后,我们分析了150例卵巢癌患者外周血样本中miR - 3135b和miR - 1273g - 3p的表达。随后,我们将它们的表达水平与100名健康对照进行了比较。在进行miRNA分离并合成miRNA特异性cDNA后,使用定量实时聚合酶链反应(qRT - PCR)技术检测miR - 3135b和miR - 1273g - 3p表达的差异。与BRCA阴性患者和健康病例相比,BRCA1/2检测呈阳性的卵巢癌患者中miR - 3135b和miR - 1273g - 3p更高。与健康病例相比,卵巢癌患者中miR - 3135b的水平显示出约4.82倍的增加,而miR - 1273g - 3p的表达则显示出约6.77倍的增加。受试者工作特征(ROC)分析表明,miR - 3135b和miR - 1273g - 3p有潜力作为区分卵巢癌患者和健康对照的标志物。miR - 3135b和miR - 1273g - 3p的高表达可能与卵巢癌的发生有关。此外,miR - 3135b可能具有诊断潜力,而miR - 1273g - 3p在卵巢癌细胞分化中可能具有诊断和预后潜力。STRING分析揭示了miR - 1273g - 3p与该基因之间的关联,表明可能通过肿瘤抑制基因的蛋白酶体降解与肿瘤形成存在潜在联系。此外,分析表明miR - 1273g - 3p与一个参与检查点介导的细胞周期停滞的基因有关。STRING分析还表明miR - 3135b与该基因相关,导致肿瘤发生级联反应的激活。总之,miR - 1273g - 3p和miR - 3135b作为诊断标志物具有显著潜力。然而,需要进一步研究以在更大的队列中全面研究这些miRNA的诊断和预测特征。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c6b/10792459/5344c62c1110/gr1.jpg

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