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探索与卵巢癌细胞顺铂耐药相关的微小RNA谱。

Exploring miRNA profile associated with cisplatin resistance in ovarian cancer cells.

作者信息

Alghamian Yaman, Soukkarieh Chadi, Aljapawe Abdulmunim, Murad Hossam

机构信息

Department of Animal Biology, Faculty of Sciences, Damascus University, Syria.

Department of Molecular and Biotechnology, Atomic Energy Commission of Syria (AECS), Syria.

出版信息

Biochem Biophys Rep. 2024 Dec 26;41:101906. doi: 10.1016/j.bbrep.2024.101906. eCollection 2025 Mar.

Abstract

Ovarian cancer is a common and lethal malignancy among women, whereas chemoresistance is one of the major challenges to its treatment and prognosis. Chemoresistance is a multifactorial phenomenon, involving various mechanisms that collectively modify the cell's response to treatment. Among the changes that arise in cells after acquiring chemoresistance is miRNA dysregulation. Here, this study aimed to identify miRNAs expression changes related to cisplatin resistance in ovarian cancer cells. The miRNA expression profiles of a cisplatin-sensitive A2780 cell line and two cisplatin-resistant cell lines, A2780cis and SK-OV-3, were analyzed using PCR array and qPCR. Accordingly, the miRNAs that were differentially expressed were further investigated to identify their biological functions and the target pathways using Gene Ontology (GO) annotation and KEGG pathway analyses. In order to evaluate the clinical significance of the differentially expressed miRNAs, survival analysis was carried out using expression data for ovarian cancer patients available in the Kaplan-Meier (KM) plotter database. The current work demonstrates that Nine miRNAs were found to be upregulated in cells resistant to cisplatin. Clearly, these miRNAs have functions in cell death/survival related processes and treatment response. They may also target pathways involved in treatment response like PI3K-Akt, pathway in cancer and MAPK. Interestingly, High expression of hsa-miR-133b, hsa-miR-512-are, hsa-miR-200b-3p, and hsa-miR-451a is related to poor overall survival in patients diagnosed with ovarian cancer. Our findings suggest that hsa-miR-133b, hsa-miR-512-5p, hsa-miR-200b-3p, and hsa-miR-451a are good candidates for future studies aimed to establishing functional links and exploring therapeutic interventions to overcome cisplatin resistance.

摘要

卵巢癌是女性中常见的致命恶性肿瘤,而化疗耐药是其治疗和预后的主要挑战之一。化疗耐药是一种多因素现象,涉及多种共同改变细胞对治疗反应的机制。细胞获得化疗耐药后出现的变化之一是微小RNA(miRNA)失调。在此,本研究旨在确定卵巢癌细胞中与顺铂耐药相关的miRNA表达变化。使用PCR芯片和定量PCR(qPCR)分析了顺铂敏感的A2780细胞系以及两个顺铂耐药细胞系A2780cis和SK-OV-3的miRNA表达谱。据此,对差异表达的miRNA进行进一步研究,通过基因本体论(GO)注释和京都基因与基因组百科全书(KEGG)通路分析来确定其生物学功能和靶标通路。为了评估差异表达miRNA的临床意义,利用卡普兰-迈耶(KM)绘图仪数据库中可用的卵巢癌患者表达数据进行生存分析。目前的研究表明,发现9种miRNA在顺铂耐药细胞中上调。显然,这些miRNA在细胞死亡/存活相关过程和治疗反应中发挥作用。它们还可能靶向参与治疗反应的通路,如PI3K-Akt、癌症通路和丝裂原活化蛋白激酶(MAPK)通路。有趣的是,hsa-miR-133b、hsa-miR-512-5p、hsa-miR-200b-3p和hsa-miR-451a的高表达与卵巢癌患者较差的总生存期相关。我们的研究结果表明,hsa-miR-133b、hsa-miR-512-5p、hsa-miR-200b-3p和hsa-miR-451a是未来旨在建立功能联系和探索克服顺铂耐药治疗干预措施研究的良好候选对象。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a613/11741906/c41de6c89be5/gr1.jpg

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