miR-16-5p enhances sensitivity to RG7388 through targeting PPM1D expression(WIP1)in Childhood Acute Lymphoblastic Leukemia

作     者：Maryam Zanjirband Soheila Rahgozar Narges Aberuyi 

作者机构：Department of Cell and Molecular Biology&MicrobiologyFaculty of Biological Science and TechnologyUniversity of IsfahanIsfahan 15100Iran. 

出 版 物：《Cancer Drug Resistance》 (癌症耐药（英文）)

年 卷 期：2023年第6卷第2期

页      面：242-256页

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：This work was supported by the University of Isfahan(96/100000/4000) 

主　　题：Pediatric ALL miR-16-5p RG7388 PPM1D p53 

摘      要：Aim:Given the encouraging results of the p53-Mdm2 inhibitor RG7388 in clinical trials and the vital function of miR-16-5p in suppressing cell proliferation,the aim of the present study was to investigate the combined impact of RG7388 and miR-16-5p overexpression on the childhood acute lymphoblastic leukemia(chALL).Methods:miRTarBase and miRDB,along with KEGG and STRING databases,were used to predict miR-16-5p target genes and explore protein-protein interaction networks,respectively.B-and T-lymphoblastic cell lines,in addition to patient primary cells,were treated with *** overexpression of miR-16-5p in Nalm6 cell line was induced through cell electroporation and transfection of microRNA mimics was confirmed by *** viability was evaluated using the MTT *** blot analyses were performed to evaluate the effects of RG7388 and miR-16-5p upregulation on the protein levels of p53 and its downstream target genes in chALL *** sample t-test was employed for statistical ***:MTT assay showed RG7388-induced cytotoxicity in wild-type p53 Nalm6 cell line and p53 functional patient primary ***,CCRF-CEM and p53 non-functional leukemic cells indicated drug *** blot analyses validated the bioinformatics results,confirming the downregulation of WIP1,p53 stabilization,as well as overexpression of p21WAF1 and Mdm2 proteins in Nalm6 cells transfected with ***,enhanced sensitivity to RG7388 was observed in the transfected ***:This is the first study indicating the mechanistic importance of miR-16-5p overexpression in chALL and its inhibitory role in leukemia treatment when combined with the p53-Mdm2 antagonist,*** findings might be useful for researchers and clinicians to pave the way for better management of chALL.