Bioinformatics Analysis of Choriocarcinoma-Related MicroRNA-Transcription Factor-Target Gene Regulatory Networks and Validation of Key miRNAs

Abstract

Objective The aim of the current research was to construct a miRNA-transcription factor (TF)-target gene regulatory network in order to investigate the mechanism underlying choriocarcinoma and to verify the network through the overexpression or silencing of hub miRNAs in vitro. Materials and Methods A mRNA expression dataset and two miRNA expression datasets were analysed to identify differentially expressed genes (DEGs) and miRNAs (DEMs) between normal cells and choriocarcinoma cells. The top 400 upregulated and downregulated DEGs were identified as candidate DEGs, which were then mapped to construct protein–protein interaction (PPI) networks and select hub genes. Moreover, the DGIdb database was utilized to select candidate drugs for hub genes. Moreover, DEM target genes were predicted through the miRWalk2.0 database and overlaid with candidate DEGs to identify the differentially expressed target genes (DETGs). Furthermore, we established miRNA-TF-target gene regulatory networks and performed functional enrichment analysis of hub DEMs. Finally, we transfected mimics or inhibitors of hub DEMs into choriocarcinoma cells and assessed cell proliferation and migration to verify the vital role of hub DEMs in choriocarcinoma. Results A total of 140 DEMs and 400 candidate DEGs were screened from choriocarcinoma cells and normal cells. A PPI network of 400 candidate DEGs was established. Twenty-nine hub genes and 99 associated small molecules were identified to provide potential target drugs for choriocarcinoma treatment. We obtained 70 DETGs of DEMs derived from the intersection between predicted miRNA target genes and candidate DEGs. Subsequently, 3 hub DEMs were selected, and miRNA-TF-target gene regulatory networks containing 4 TFs, 3 TFs and 3 TFs for each network were constructed. The RT-PCR results confirmed that miR-29b-3p was highly expressed and that miR-519c-3p and miR-520a-5p were expressed at low levels in choriocarcinoma cells. The overexpression or silencing results suggested that 3 dysregulated hub DEMs jointly accelerated the proliferation and migration of choriocarcinoma. Conclusion Association of miRNA-TF-target gene regulatory networks may help us explore the underlying mechanism and provide potential targets for the diagnosis and treatment of choriocarcinoma.

METTL3 promotes choriocarcinoma progression by activating the miR‐935/GJA1 pathway in an m6A‐dependent manner

“…It is therefore urgent to investigate potential targets related to CCA progression for CCA therapy. Increasing evidence demonstrates that miRNAs have altered expression properties during CCA progression 21 . Unfortunately, the mechanism of miRNAs regulating CCA development has not been systematically elucidated.…”

“…Increasing evidence demonstrates that miRNAs have altered expression properties during CCA progression. 21 Unfortunately, the mechanism of miRNAs regulating CCA development has not been systematically elucidated. This work investigated the role of miR-935 in CCA cell phenotypes and the detailed mechanism using CCA cell lines and tumor-bearing nude mouse model.…”

“…A previous study has reported that miR-935 expression is the highest in choriocarcinoma samples among the 140 candidate differently expressed miRNAs that were analyzed through the GEO database (GEO accession GSE130489) and identified by Venn diagram analysis in comparison with controls. 21 Thus, our work employed miR-935 as a study subject. The expression of miR-935 was first investigated in CCA tissues and cells.…”

Integrative analysis links autophagy to intrauterine adhesion and establishes autophagy-related circRNA-miRNA-mRNA regulatory network

“…In order to explore the target drugs of ARDEGs, the drug-gene interaction database (DGIdb, https://dgidb.genome.wustl.edu/ ) was adopted, which is the online tool for drug-gene predication. Finally, Cytoscape was utilized to construct the drug- ARDEGs network as previously described [ 20 ].…”

“…genome.wustl.edu/) was adopted, which is the online tool for drug-gene predication. Finally, Cytoscape was utilized to construct the drug-ARDEGs network as previously described [20].…”