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Determination of the WWOX gene function in modulating cellular pathways activated by AP-2α and AP-2γ transcription factors in bladder cancer

ABSTRACT: Determination of the WWOX gene function in modulating cellular pathways activated by AP-2α and AP-2γ transcription factors in bladder cancer

PROVIDER: PRJNA797083 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR17613075.fastq.gz	Fastqsanger.gz
	SRR17613076.fastq.gz	Fastqsanger.gz
	SRR17613077.fastq.gz	Fastqsanger.gz
	SRR17613078.fastq.gz	Fastqsanger.gz
	SRR17613079.fastq.gz	Fastqsanger.gz

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Determination of the WWOX gene function in modulating cellular pathways activated by AP-2α and AP-2γ transcription factors in bladder cancer

Project description:The aim of the current study was to investigate how various levels of WWOX, AP-2α and AP-2γ affect signaling pathways in bladder cancer cell lines. Global transcriptome analysis using CAGE-seq was conducted.

2022-01-17 | GSE193659 | GEO

Determination of WWOX Function in Modulating Cellular Pathways Activated by AP-2α and AP-2γ Transcription Factors in Bladder Cancer.

Project description:Following the invention of high-throughput sequencing, cancer research focused on investigating disease-related alterations, often inadvertently omitting tumor heterogeneity. This research was intended to limit the impact of heterogeneity on conclusions related to WWOX/AP-2α/AP-2γ in bladder cancer which differently influenced carcinogenesis. The study examined the signaling pathways regulated by WWOX-dependent AP-2 targets in cell lines as biological replicates using high-throughput sequencing. RT-112, HT-1376 and CAL-29 cell lines were subjected to two stable lentiviral transductions. Following CAGE-seq and differential expression analysis, the most important genes were identified and functionally annotated. Western blot was performed to validate the selected observations. The role of genes in biological processes was assessed and networks were visualized. Ultimately, principal component analysis was performed. The studied genes were found to be implicated in MAPK, Wnt, Ras, PI3K-Akt or Rap1 signaling. Data from pathways were collected, explaining the differences/similarities between phenotypes. FGFR3, STAT6, EFNA1, GSK3B, PIK3CB and SOS1 were successfully validated at the protein level. Afterwards, a definitive network was built using 173 genes. Principal component analysis revealed that the various expression of these genes explains the phenotypes. In conclusion, the current study certified that the signaling pathways regulated by WWOX and AP-2α have more in common than that regulated by AP-2γ. This is because WWOX acts as an EMT inhibitor, AP-2γ as an EMT enhancer while AP-2α as a MET inducer. Therefore, the relevance of AP-2γ in targeted therapy is now more evident. Some of the differently regulated genes can find application in bladder cancer treatment.

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Genome-wide identification of AP-2α by ChIP-chip in breast cancer cell line MCF7

Project description:The AP-2 family of transcription factors is involved in the regulation of embryonic development, cell proliferation and tumorigenesis. To date, five members of the AP-2 family have been identified: AP-2α, AP-2β, AP-2γ, AP-2δ and AP-2ε. All AP-2 proteins bind as homo- or heterodimers to the consensus sequence of 5'- GCCNNNGGC-3' and directly regulate transcription of their target genes. Among these, AP-2α is the best-characterized gene.

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Project description:Overexpression of the AP-2γ transcription factor in breast tumours has been identified as an independent predictor of poor outcome and failure of hormone therapy, even in ER positive, ErbB2 negative tumours; markers of a more favourable prognosis. To understand further the role of AP-2γ in breast carcinoma, we have used an RNA interference and gene expression profiling strategy using the MCF-7 cell line as a model for ER positive, ErbB2 negative tumours with AP-2γ overexpression. Gene expression changes between control and silenced cells implicate AP-2γ in the control of cell cycle progression and developmental signalling. Keywords: RNA interference

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Project description:Mammary gland ductal morphogenesis depends on the differentiation of mammary stem cells (MaSCs) into basal and luminal lineages. The AP-2γ transcription factor, encoded by Tfap2c, has a central role in mammary gland development but its effect in mammary lineages and specifically MaSCs is largely unknown. Herein, we utilized an inducible, conditional knockout of Tfap2c to elucidate the role of AP-2γ in maintenance and differentiation of MaSCs. Loss of AP-2γ in the basal epithelium profoundly altered the transcriptomes and decreased the number of cells within several clusters of mammary epithelial cells, including adult MaSCs and luminal progenitors. AP-2γ regulated the expression of genes known to be required for mammary development including Cebpb, Nfkbia, and Rspo1. As a result, AP-2γ-deficient mice exhibited repressed mammary gland ductal outgrowth and inhibition of regenerative capacity. The findings demonstrate that AP-2γ can regulate development of mammary gland structures potentially regulating maintenance and differentiation of multipotent MaSCs.

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Project description:TFAP2A (AP-2α) is a member of the transcription factor AP-2 family, functions as a tumor suppressor by regulating the expression of various cancer-related genes; its expression is positively correlated with chemosensitivity and survival of cancer patients.

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Genome-wide identification of AP-2α targets in bladder cells by RNA-seq (Control vs AP-2α OE)

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AP-2α pull down from E12.5 cortex

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