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TAp63-regulated microRNAs suppress cutaneous squamous cell carcinoma

ABSTRACT: TAp63-regulated microRNAs suppress cutaneous squamous cell carcinoma

PROVIDER: PRJNA609900 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11195858.fastq.gz	Fastqsanger.gz
	SRR11195859.fastq.gz	Fastqsanger.gz
	SRR11195860.fastq.gz	Fastqsanger.gz
	SRR11195861.fastq.gz	Fastqsanger.gz
	SRR11195862.fastq.gz	Fastqsanger.gz

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TAp63-regulated microRNAs suppress cutaneous squamous cell carcinoma

Project description:TAp63 is a transcription factor belonging to the p53 family with important tumor suppressive functions. We show that TAp63-/- mice exhibit an increased susceptibility to UVR-induced cutaneous squamous cell carcinoma (cuSCC). These tumors showed global disruption of miRNA and mRNA expression when compared to tumors arising in wild-type mice. A comparison to similarly sequenced human cuSCC tumors identified miR-30c-2* and miR-497 as being significantly underexpressed in cuSCC. Reintroduction of these miRNAs significantly inhibited the growth of cuSCC cell lines and xenografts. Proteomic profiling of cells transfected with either miRNA showed significant downregulation of proteins related to cell cycle progression and mitosis. A cross-platform comparison of the RNAseq and proteomics signatures identified 7 downregulated proteins, which are also frequently overexpressed in both mouse and human cuSCC. Knockdown of AURKA, KIF18B, PKMYT1, and ORC1 in cuSCC cell lines suppressed tumor cell proliferation and induced cell death. Additionally, we found that an investigational, oral, selective inhibitor of AURKA suppressed cuSCC cell growth and induced cell death, and showed anti-tumor effects in vivo. Our data establishes TAp63 as an essential regulator of miRNA expression during skin carcinogenesis and reveals a novel network of miRNAs and mRNAs, which include potential targets for therapeutic intervention.

2020-07-07 | PXD014261 | Pride

TAp63-regulated microRNAs suppress cutaneous squamous cell carcinoma [miRNA-seq]

Project description:TAp63-regulated microRNAs suppress cutaneous squamous cell carcinoma [miRNA-seq]

| PRJNA609173 | ENA

TAp63-regulated microRNAs suppress cutaneous squamous cell carcinoma [RNA-seq]

Project description:TAp63-regulated microRNAs suppress cutaneous squamous cell carcinoma [RNA-seq]

| PRJNA609904 | ENA

TAp63-regulated microRNAs suppress cutaneous squamous cell carcinoma [RNA-seq]

Project description:The goal of this study is to compare the differences in the global mRNA expression of WT and TAp63-/- skin and SCC TAp63 is a p53 family member and potent tumor and metastasis suppressor. Here, we show that TAp63-/- mice exhibit an increased susceptibility to UVR- induced cutaneous squamous cell carcinoma (cuSCC). A human-to-mouse comparison of cuSCC tumors identified miR-30c-2* and miR-497 as underexpressed in TAp63-deficient cuSCC. Reintroduction of these microRNAs significantly inhibited the growth of cuSCC cell lines and tumors. Proteomic profiling of cells expressing either microRNA showed downregulation of cell cycle progression and mitosis associated proteins. A mouse to human and cross- platform comparison of RNA-Seq and proteomics data identified a 7-gene signature, including AURKA, KIF18B, PKMYT1, and ORC1, which were overexpressed in cuSCC. Knockdown of these factors in cuSCC cell lines suppressed tumor cell proliferation and induced apoptosis. Additionally, selective inhibition of AURKA suppressed cuSCC cell proliferation, induced apoptosis, and showed anti-tumor effects in vivo. Finally, treatment with miR-30c-2* or miR-497 microRNA mimics was highly effective in suppressing cuSCC growth in vivo. Our data establishes TAp63 as an essential regulator of novel microRNAs that can be therapeutically targeted for potent suppression of cuSCC.

2020-03-04 | GSE146257 | GEO

TAp63-regulated microRNAs suppress cutaneous squamous cell carcinoma [miRNA-seq]

Project description:The goal of this study is to compare the differences in the global miRNA expression of WT and TAp63-/- skin and SCC

2020-02-28 | GSE146079 | GEO

TAp63-regulated microRNAs suppress cutaneous squamous cell carcinoma

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-03-04 | GSE146258 | GEO

FANCD2 Activates Transcription of TAp63 and Suppresses Tumorigenesis

Project description:Fanconi Anemia (FA) is a rare genetic disorder characterized by an increased susceptibility to squamous cell cancers. Fifteen FA genes are known, and the encoded proteins cooperate in a common DNA repair pathway. A critical step is the monoubiquitination of the FANCD2 protein, and cells from most FA patients are deficient in this step. How monoubiquitinated FANCD2 suppresses squamous cell cancers is unknown. Here we show that Fancd2-deficient mice are prone to Ras oncogene-driven skin carcinogenesis, while Usp1-deficient mice, expressing elevated cellular levels of Fancd2-Ub, are resistant to skin tumors. Moreover, Fancd2-Ub activates the transcription of the tumor suppressor TAp63, thereby promoting cellular senescence and blocking skin tumorigenesis. For FA patients, the reduction of FANCD2-Ub and TAp63 protein levels may account for their susceptibility to squamous cell neoplasia. Taken together, Usp1 inhibition may be a useful strategy for upregulating TAp63 and preventing or treating squamous cell cancers in the general non-FA population. Examination of FANCD2 binding after UV treatment in 293T cells

2013-06-27 | E-GEOD-46902 | biostudies-arrayexpress

FANCD2 Activates Transcription of TAp63 and Suppresses Tumorigenesis

2013-06-27 | GSE46902 | GEO

TAp63 in pancreas cancer predicts the squamous subtype and promotes a suppressive immune micromilleu

Project description:To evaluate the role of aberrant TAp63 in PDAC, we analyzed transcriptomics by RNAseq in the TAp63 and deltaNP63 over-expressing pancreatic cancer cells.

2022-11-22 | GSE218268 | GEO

Microarray analysis of microRNA expression in cutaneous squamous cell carcinoma

Project description:MicroRNAs (miRNAs) are a novel class of short RNAs which have shown to be dysregulated in a variety of cancers including squamous cell carcinoma (SCC) of the head&neck. Microarray based miRNA expression profiles of cutaneous SCC (cSCC) however have not been investigated so far. Seven patients with cutaneous SCC were enrolled in the study. Tumor biopsies (n=7) were taken from the center of the tumor. Adjacent healthy skin (n=7) was biopsied as a control (intraindividual control). miRNA expression profiles of all specimen were detected by mircroarray miRNA expression profiling based on miRBAse 16 and compared.

2012-10-08 | GSE34536 | GEO

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