Effects of forkhead box protein A1 knockout on microRNA expression profiles of benzoapyrene malignant transformed cells THBEc1
10.3867/j.issn.1000-3002.2025.03.002
- VernacularTitle:FOXA1敲除对苯并[a]芘恶性转化细胞THBEc1 miRNA表达谱的影响
- Author:
Zhiyu LIU
1
;
Yujin FU
1
;
Yitong LIN
1
;
Juanling FU
1
;
Biyun YAO
1
;
Peng ZHAO
1
Author Information
1. 北京大学公共卫生学院毒理学系,食品安全毒理学研究与评价北京市重点实验室,北京 100191
- Publication Type:Journal Article
- Keywords:
benzo[a]pyrene;
forkhead box protein A1;
microRNA;
benzo[a]pyrene malignant trans-formed cells
- From:
Chinese Journal of Pharmacology and Toxicology
2025;39(3):169-182
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To explore the potential mechanisms of forkhead box protein A1(FOXA1)in benzo[a]pyrene(BaP)-induced carcinogenesis by investigating the effect of FOXA1 by knockout on microRNA(miRNA)expression profiles in BaP malignant transformed cells THBEc1 and establishing regulatory networks between FOXA1,miRNA and their target genes.METHODS FOXA1 knockout THBEc1 cells THBEc1-ΔFOXA1-c34 and control cells THBEc1-ctrl were used as study models.Western blotting was employed to determine FOXA1 protein expression levels.Next-generation sequencing(NGS)tech-nology was used to identify differentially expressed miRNAs between THBEc1-ΔFOXA1-c34 and THBEc1-ctrl cells,with subsequent validation by RT-qPCR.Five databases(ENCORI,miRDB,mirDIP,miRWalk and TargetScan 8.0)were used in conjunction with NGS results of mRNA between THBEc1-ΔFOXA1-c34 and THBEc1-ctrl to predict different expressed genes(DEGs)regulated by the identified differentially expressed miRNAs.GO and KEGG enrichment analyses were conducted on the DEGs using the DAVID database.Interaction network analysis of the proteins encoded by the DEGs was performed using STRING 12.0 and Cytoscape 3.10.2 software.RESULTS No FOXA1 expression was detected in THBEc1-ΔFOXA1-c34 cells.A differential analysis of miRNA expressions revealed 33 miRNAs with a fold change of＞2 or＜0.5 and a false discovery rate of＜0.05 between THBEc1-ΔFOXA1-c34 and THBEc1-ctrl cells,13 of which were down-regulated and 20 were up-regulated in THBEc1-ΔFOXA1-c34 cells.A regulatory network was formed by 11 down-regulated miRNAs and 32 up-regulated mRNAs,while a second network included 16 up-regulated miRNAs and 56 down-regulated mRNAs.The 27 differentially expressed miRNAs participated in various biological processes through the regulation of 88 DEGs,primarily associated with cell growth,proliferation,migration,apoptosis,angiogenesis,epithe-lial-mesenchymal transition,and signal transduction(TGF-β,Hippo,NF-kappa B and MAPK pathways).CONCLUSION The miRNA expression profile in BaP-malignant transformed THBEc1 cells is altered following FOXA1 knockout that may disrupt TGF-β and MAPK signaling pathways by changing miRNA expression levels,thereby inhibiting cell proliferation and migration.
