铂类药物的分子网络及其与癌症中 microRNAs 的相互作用。

Molecular Networks of Platinum Drugs and Their Interaction with microRNAs in Cancer.

机构信息

Division of Risk Assessment, Center for Biological Safety and Research, National Institute of Health Sciences, Kawasaki 210-9501, Japan.

Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, Tokyo 113-0033, Japan.

出版信息

Genes (Basel). 2023 Nov 13;14(11):2073. doi: 10.3390/genes14112073.

DOI:10.3390/genes14112073

PMID:38003016

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10671144/

Abstract

The precise mechanism of resistance to anti-cancer drugs such as platinum drugs is not fully revealed. To reveal the mechanism of drug resistance, the molecular networks of anti-cancer drugs such as cisplatin, carboplatin, oxaliplatin, and arsenic trioxide were analyzed in several types of cancers. Since diffuse-type stomach adenocarcinoma, which has epithelial-mesenchymal transition (EMT)-like characteristics, is more malignant than intestinal-type stomach adenocarcinoma, the gene expression and molecular networks in diffuse- and intestinal-type stomach adenocarcinomas were analyzed. Analysis of carboplatin revealed the causal network in diffuse large B-cell lymphoma. The upstream regulators of the molecular networks of cisplatin-treated lung adenocarcinoma included the anti-cancer drug trichostatin A (TSA), a histone deacetylase inhibitor. The upstream regulator analysis of cisplatin revealed an increase in FAS, BTG2, SESN1, and CDKN1A, and the involvement of the tumor microenvironment pathway. The molecular networks were predicted to interact with several microRNAs, which may contribute to the identification of new drug targets for drug-resistant cancer. Analysis of oxaliplatin, a platinum drug, revealed that the SPINK1 pancreatic cancer pathway is inactivated in ischemic cardiomyopathy. The study showed the importance of the molecular networks of anti-cancer drugs and tumor microenvironment in the treatment of cancer resistant to anti-cancer drugs.

摘要

抗癌药物（如铂类药物）耐药的确切机制尚未完全揭示。为了揭示耐药机制，对顺铂、卡铂、奥沙利铂和三氧化二砷等几种抗癌药物的分子网络进行了分析。由于具有上皮-间充质转化（EMT）样特征的弥漫型胃腺癌比肠型胃腺癌更具恶性，因此对弥漫型和肠型胃腺癌进行了基因表达和分子网络分析。卡铂分析揭示了弥漫性大 B 细胞淋巴瘤的因果网络。顺铂处理的肺腺癌分子网络的上游调节剂包括抗癌药物曲古抑菌素 A（TSA），一种组蛋白去乙酰化酶抑制剂。顺铂的上游调控分析显示 FAS、BTG2、SESN1 和 CDKN1A 的增加，以及肿瘤微环境途径的参与。预测分子网络与几种 microRNAs 相互作用，这可能有助于鉴定耐药性癌症的新药物靶点。对铂类药物奥沙利铂的分析表明，SPINK1 胰腺癌途径在缺血性心肌病中失活。该研究表明抗癌药物和肿瘤微环境的分子网络在治疗抗癌药物耐药性癌症中的重要性。