Overexpression of miR-23b-3b+miR-218-5p+miR-124-3p differentially modifies the transcriptome of C-33A and CaSki cells and the regulation of cellular processes involved in the progression of cervical cancer

ABSTRACT: Dysregulation of tumor suppressor miRNAs (tsmiRs) is associated with tumor progression in cancer. miR-23b-3p, miR-218-5p and miR-124-3p are tsmiRs in cervical cancer (CC) and regulate the translation of genes involved in metastasis-related biological processes. Objective. To analyze transcriptome changes in cervical cancer cell lines (C-33A HPV-negative and CaSki HPV-positive) overexpressing miR-23b-3b+miR-218-5p+miR-124-3p, to identify specific target transcripts common to all three miRNAs, as well as signaling pathways and cellular processes related to tumor progression. Methods. The transcriptome of C-33A and CaSki cells transfected with miR-23b-3b+miR-218-5p+miR-124-3p was analyzed by RNA-seq. Differentially expressed genes (DEGs) were subjected to Gene Ontology analysis on the DAVID platform. The function of under-regulated genes was analyzed on the GEPIA 2.0, Kaplan-Meier plotter and STRING platforms. On the TargetScanHuman platform it was determined which transcripts have MREs for miR-23b-3p, miR-218-5p and/or miR-124-3p in their 3`UTR region. Results. Simultaneous overexpression of miR-218-5p, miR-124-3p and miR-23b-3p induced changes in global gene expression in C-33A and CaSki cells. In C-33A cells, DEGs included 45 over- and 172 under-regulated transcripts; in CaSki, 125 transcripts were over- and 84 under-regulated. The under-regulated transcripts enrich proliferation, migration, apoptosis and angiogenesis; 20 of these genes are associated with overall survival (OS) in women with CC, and 18 of the 20 mRNAs have MREs for one, two or all three miRNAs. Conclusions. miR-23b-3b+miR-218-5p+miR-124-3p, differentially modify global gene expression in C-33A and CaSki cells. The results indicate that these miRNAs act synergistically and modulate CC progression through individual and shared targets by two or all three miRNAs.

ORGANISM(S): Homo sapiens

PROVIDER: GSE289927 | GEO | 2025/02/24

REPOSITORIES: GEO