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Jahanafrooz, Z; Ghaffari-Tabrizi-Wizsy, N.
Regulatory effects of lncRNA PVT1 on transcriptome in human breast cancer MDA-MB-231 cell line determined by in silico analyses
CHROMOSOMA. 2025; 134(1): 5 Doi: 10.1007/s00412-025-00830-8
Web of Science PubMed FullText FullText_MUG

Co-authors Med Uni Graz: Ghaffari Tabrizi-Wizsy Nassim
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Abstract:: Overexpression or knockdown of a specific gene is usually helpful in understanding its underlying molecular mechanism. PVT1 gene is regarded as an oncogenic long non-coding RNA (lncRNA) in many cancers, including breast invasive carcinoma (BRCA). We investigated some of the underlying molecular mechanisms of PVT1 in human invasive breast cancer MDA-MB-231 cells. Differentially expressed genes (DEGs) were obtained after PVT1 overexpression and knockdown in MDA-MB-231 cells from the gene expression profiles GSE175736 and GSE97587. RNAInter database was used to predict miRNAs and TFs that have interactions with PVT1. Competing endogenous RNA (ceRNA) and transcription regulatory networks visualized using Cytoscape software. It was found that HLA-G, GBP4, SERPINE1, DHRS2, MT1X, and PRLR were common PVT1 co-upregulated and co-downregulated genes in the two datasets. SERPINE1 was identified as the most positively correlated gene with PVT1 expression in MDA-MB-231 cells. DEGs in overexpressed and silenced PVT1 cells were enriched in the cell adhesion process and JAK-STAT signaling pathway, respectively. In the ceRNA network, PVT1 acts as a competing endogenous RNA for downregulated miR-145-5p, miR-17-5p, and miR-20a-5p. PVT1/miR-145-5p/SERPINE1 was a common axis in ceRNA networks in the two datasets. SERPINIE1 was also a common node between ceRNA and transcription regulatory networks. RT-qPCR validated the anticipated levels of PVT1, miR-145-5p, and SERPINE1 in MDA-MB-231 cancer compared to MCF-10 A noncancerous cells. Taken together, the results of this work shed light on the several possible oncogenic mechanisms of PVT1, including its closely related genes and signaling pathways.
Find related publications in this database (Keywords): PVT1; CeRNA network; Transcription network; MDA-MB-231 cells