基于基因集富集分析的MLN2238对基底样乳腺癌的抑制作用研究
Inhibitory Effort of MLN2238 on Basal-Like Breast Cancer: An Investigation Based on the Gene Set Enrichment Analysis.
发表日期:2023 Jul 31
作者:
Dapeng Wang, Yunyan Li, Fushen Luo, Xue Song, Shuang Wu, Ying Chen, Na Zhang
来源:
GENES & DEVELOPMENT
摘要:
基底细胞样乳腺癌(BLBC)是一种乳腺癌亚型,具有高复发率和强侵袭性的特征。因此,有必要开发新的药物治疗BLBC。小分子药物的数据从癌症药物敏感性基因组学(GDSC)数据库中下载,小分子药物的靶基因信息从SWISS网站获得。基于TCGA数据库,利用全基因组t值测序筛选差异表达基因(DEGs)。进一步进行生物信息学分析。细胞周期使用流式细胞术确定。通过Western blot计算P21和P27的表达。采用siPLK1转染干预PLK1表达。进一步进行细胞实验技术。通过临床样本研究和体外实验验证筛选的小分子药物的具体效应和机制。MLN2238可以显著抑制基底细胞样乳腺癌细胞系HCC38的增殖。基于MLN2238显著上调的靶基因构建了PPI网络,其中PLK1是关键基因,KEGG分析显示上调的靶基因处于细胞周期中。流式细胞术显示MLN2238阻断了HCC38细胞在G2/M期。Western blot结果显示,MLN2238抑制了HCC38细胞中P21和P27的表达。基于TCGA数据库的存活热图显示,PLK1对乳腺癌的存活影响最大。PLK1表达水平高的患者总体生存率较低。体外细胞实验结果显示,siPLK1转染后PLK1表达显著降低。SiPLK1转染后细胞增殖能力显著受抑。MLN2238是治疗BLBC的潜在靶向药物,而PLK1是MLN2238抑制BLBC的靶基因。
Basal cell-like breast cancer (BLBC), one subtype of breast cancer, has the characteristics of a high recurrence rate and strong invasiveness. Therefore, it is necessary to exploit new drugs for the therapy of BLBC. The data on small molecular drugs were downloaded from the cancer drug sensitivity genomics (GDSC) database, and the target gene information of small molecular drugs was obtained from the SWISS website. Based on the TCGA database, a genome-wide t-value sequencing for screening differentially expressed genes (DEGs) was constructed. The bioinformatics analysis was further performed. The cell cycle was determined using flow cytometry. Western blot was performed to calculate the expression of P21 and P27. siPLK1 transfection was performed to interfere with PLK1 expression. And further cell experimental techniques were performed. The specific effect and mechanisms of the screened small molecular drugs were confirmed through clinical sample studies and in vitro experiments. MLN2238 could significantly inhibit the proliferation of HCC38, a BLBC cell line. The PPI network based on the target gene significantly up-regulated by MLN2238 shows that PLK1 is the key gene, and KEGG analysis shows that the up-regulated target gene is in the cell cycle. Flow cytometry showed that MLN2238 blocked HCC38 cells in the G2/M phase. The results of the Western blot revealed that MLN2238 inhibited the expression of P21 and P27 in HCC38 cells. The survival heat map based on the TCGA database shows that PLK1 has the greatest impact on the survival of breast cancer. Patients with high levels of PLK1 expression had a poorer overall survival rate than those with low levels of PLK1. Cell experiments in vitro revealed that the PLK1 expression decreased significantly after siPLK1 transfection. The ability of cell proliferation was significantly inhibited after SiPLK1 transfection. MLN2238 is a potential target drug for the therapy of BLBC, and PLK1 is the target gene for MLN2238 to inhibit BLBC.