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Total mRNA-seq to determine how the gene expression is altered in both parental and BRCA2-depleted CCNC- and MED12-KO cells.

ABSTRACT: Background: Loss of RNA Pol II transcription Mediator components like CCNC, MED12 led to improved survival of PARPi-treated and untreated BRCA2-depleted cells. Mediator is best known for its function with RNA Pol II in regulating gene transcription, we performed total mRNA-Seq with control and BRCA2-depleted CCNC- and MED12-KO cells. The aim of the present prospective study was to reveal how the gene expression is altered in both parental and BRCA2-depleted CCNC- and MED12-KO cells which might contribute to the PARPi resistance in BRCA2 depleted cells. Methods: HEK293A BRCA2 CKI mAID-EGFP WT, CCNC-KO, and MED12-KO with or without BRCA2 depletion cells (each with two biological replicates) were collected and total RNA was extracted and subjected to RNA-seq at HiSeq3000 (Illumina). Results: Based on the transcriptomic data, we examined differentially expressed genes and performed KEGG pathway enrichment analysis.The results suggested that in both control and BRCA2-depleted CCNC- and MED12-knockout cells, several signaling pathways like the transforming growth factor (TGF)-beta signaling pathway and extracellular matrix (ECM)-receptor interaction pathway et al were activated which probably facilitate cell proliferation upon BRCA2 loss. Conclusions: Our results imply that TGF-beta signaling and other signaling pathways such as the ECM-receptor interaction pathway which play roles in the regulation of cellular functions such as proliferation, adhesion, apoptosis, differentiation and migration, may together contribute to the involvement of CCNC and MED12 in drug resistance.

ORGANISM(S): Homo sapiens

PROVIDER: GSE150067 | GEO | 2021/05/06

REPOSITORIES: GEO

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