PXD014261

PXD014261 is an original dataset announced via ProteomeXchange.

Title	TAp63-regulated microRNAs suppress cutaneous squamous cell carcinoma
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.
HostingRepository	PRIDE
AnnounceDate	2020-07-07
AnnouncementXML	Submission_2020-07-06_21:59:00.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD014261
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	John Koomen
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex; Oxidation; Carbamidomethyl
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-06-14 08:16:17	ID requested
⏵ 1	2020-07-06 21:59:01	announced

Davis AJ, Tsinkevich M, Rodencal J, Abbas HA, Su XH, Gi YJ, Fang B, Rajapakshe K, Coarfa C, Gunaratne PH, Koomen JM, Tsai KY, Flores ER, TAp63-Regulated miRNAs Suppress Cutaneous Squamous Cell Carcinoma through Inhibition of a Network of Cell-Cycle Genes. Cancer Res, 80(12):2484-2497(2020) [pubmed]

submitter keyword: p63, microRNA, Cutaneous Squamous Cell Carcinoma, Expression Proteomics

Elsa Flores, PhD
contact affiliation	Moffitt Cancer Center Tampa, FL, USA
contact email	elsa.flores@moffitt.org
lab head
John Koomen
contact affiliation	Moffitt Cancer Center
contact email	john.koomen@moffitt.org
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD014261
     1. Label: PRIDE project
     2. Name: TAp63-regulated microRNAs suppress cutaneous squamous cell carcinoma