Sriram Navneeth, Mukherjee Sunny, Sah Mahesh Kumar
Department of Biotechnology, Dr. B. R. Ambedkar National Institute of Technology, Jalandhar, Punjab 144011 India.
3 Biotech. 2022 Jul;12(7):146. doi: 10.1007/s13205-022-03207-1. Epub 2022 Jun 10.
The interrelation of cancer and Alzheimer's disorder (AD)-associated molecular mechanisms, reported last decade, paved the path for drug discoveries. In this direction, while chemotherapy is well established for breast cancer (BC), the detection and targeted therapy for AD is not advanced due to a lack of recognized peripheral biomarkers. The present study aimed to find diagnostic and prognostic molecular signature markers common to both BC and AD for possible drug targeting and repurposing. For these disorders, two corresponding microarray datasets (GSE42568, GSE33000) were used for identifying the differentially expressed genes (DEGs), resulting in recognition of CD209 and MCM7 as the two common players. While the CD209 gene was upregulated in both disorders and has been studied vastly, the MCM7 gene showed a strikingly reverse pattern of expression level, downregulated in the case of BC while upregulated in the case of AD. Thus, the MCM7 gene was further analyzed for expression, predictions, and validations of its structure and protein-protein interaction (PPI) for the possible development of new treatment methods for AD. The study concluded with indicative drug repurposing studies to check the effect of existing clinically approved drugs for BC for rectifying the expression levels of the mutated MCM7 gene in AD.
The online version contains supplementary material available at 10.1007/s13205-022-03207-1.
过去十年报道的癌症与阿尔茨海默病(AD)相关分子机制的相互关系为药物发现铺平了道路。在这个方向上,虽然乳腺癌(BC)的化疗已很成熟,但由于缺乏公认的外周生物标志物,AD的检测和靶向治疗并不先进。本研究旨在寻找BC和AD共有的诊断和预后分子特征标志物,以便进行可能的药物靶向和重新利用。对于这些疾病,使用了两个相应的微阵列数据集(GSE42568、GSE33000)来识别差异表达基因(DEG),结果识别出CD209和MCM7是两个共同因素。虽然CD209基因在两种疾病中均上调且已被广泛研究,但MCM7基因显示出明显相反的表达水平模式,在BC中下调而在AD中上调。因此,对MCM7基因进行了进一步分析,以研究其表达、预测及其结构和蛋白质-蛋白质相互作用(PPI)的验证,以便可能开发AD的新治疗方法。该研究最后进行了指示性药物重新利用研究,以检查现有的BC临床批准药物对纠正AD中突变MCM7基因表达水平的效果。
在线版本包含可在10.1007/s13205-022-03207-1获取的补充材料。