多柔比星可下调乳腺癌细胞的细胞周期调控中枢基因。

IF 2.8 4区 医学 Q2 ONCOLOGY
Mano Chitra Karthikeyan, Chandhru Srinivasan, Kowsika Prabhakar, Priyadharshini Manogar, Abirami Jayaprakash, Antony Joseph Velanganni Arockiam
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引用次数: 0

摘要

乳腺癌(BC)是世界上最常见的癌症,其发病机制复杂。目前迫切需要揭示作为潜在治疗靶点的关键基因,这对推进乳腺癌的治疗至关重要。本研究试图调查多柔比星(DOX)对通过生物信息学分析获得的众多乳腺癌数据集中已确定的关键基因的影响。迄今为止,已对基因表达总库(GEO)中公开可用的阵列表达谱编码数据集进行了荟萃分析。使用 GEO2R 鉴定的差异表达基因(DEGs)显示,在三个平台(GPL570、GPL6244 和 GPL17586)的数据集中,共有 23 个常见的 DEGs,包括 9 个上调基因和 14 个下调基因,而且在 KEGG 分析中,常见的上调 DEGs 在细胞周期中表现出显著的富集。在细胞视图程序中,NUSAP1、CENPF、TPX2、PRC1、ANLN、BUB1B、AURKA、CCNB2和CDK-1这九个基因的度值和MCODE得分较高,被认为是枢纽基因。经 GEPIA 和 UALCAN 数据库验证,这些枢纽基因在 BC 所有亚类的疾病状态中普遍被激活,并与 BC 患者的总生存期相关。qRT-PCR 证实,DOX 治疗会导致 BC 细胞系中这些基因的表达减少,这进一步证明 DOX 仍是治疗 BC 的有效药物,并表明开发多柔比星的改良配方以减少毒性和耐药性,可提高其作为 BC 有效疗法的疗效。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Doxorubicin downregulates cell cycle regulatory hub genes in breast cancer cells.

Doxorubicin downregulates cell cycle regulatory hub genes in breast cancer cells.

Breast cancer (BC) is the leading commonly diagnosed cancer in the world, with complex mechanisms underlying its development. There is an urgent need to enlighten key genes as potential therapeutic targets crucial to advancing BC treatment. This study sought to investigate the influence of doxorubicin (DOX) on identified key genes consistent across numerous BC datasets obtained through bioinformatic analysis. To date, a meta-analysis of publicly available coding datasets for expression profiling by array from the Gene Expression Omnibus (GEO) has been carried out. Differentially Expressed Genes (DEGs) identified using GEO2R revealed a total of 23 common DEGs, including nine upregulated genes and 14 downregulated genes among the datasets of three platforms (GPL570, GPL6244, and GPL17586), and the commonly upregulated DEGs, showed significant enrichment in the cell cycle in KEGG analysis. The top nine genes, NUSAP1, CENPF, TPX2, PRC1, ANLN, BUB1B, AURKA, CCNB2, and CDK-1, with higher degree values and MCODE scores in the cytoscape program, were regarded as hub genes. The hub genes were activated in disease states commonly across all the subclasses of BC and correlated with the unfavorable overall survival of BC patients, as verified by the GEPIA and UALCAN databases. qRT-PCR confirmed that DOX treatment resulted in reduced expression of these genes in BC cell lines, which reinforces the evidence that DOX remains an effective drug for BC and suggests that developing modified formulations of doxorubicin to reduce toxicity and resistance, could enhance its efficacy as an effective therapeutic option for BC.

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来源期刊
Medical Oncology
Medical Oncology 医学-肿瘤学
CiteScore
4.20
自引率
2.90%
发文量
259
审稿时长
1.4 months
期刊介绍: Medical Oncology (MO) communicates the results of clinical and experimental research in oncology and hematology, particularly experimental therapeutics within the fields of immunotherapy and chemotherapy. It also provides state-of-the-art reviews on clinical and experimental therapies. Topics covered include immunobiology, pathogenesis, and treatment of malignant tumors.
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