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PXD014261

PXD014261 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleTAp63-regulated microRNAs suppress cutaneous squamous cell carcinoma
DescriptionTAp63 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.
HostingRepositoryPRIDE
AnnounceDate2020-07-07
AnnouncementXMLSubmission_2020-07-06_21:59:00.xml
DigitalObjectIdentifierhttps://dx.doi.org/10.6019/PXD014261
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterJohn Koomen
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListTMT6plex; Oxidation; Carbamidomethyl
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02019-06-14 08:16:17ID requested
12020-07-06 21:59:01announced
Publication List
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]
Keyword List
submitter keyword: p63, microRNA, Cutaneous Squamous Cell Carcinoma, Expression Proteomics
Contact List
Elsa Flores, PhD
contact affiliationMoffitt Cancer Center Tampa, FL, USA
contact emailelsa.flores@moffitt.org
lab head
John Koomen
contact affiliationMoffitt Cancer Center
contact emailjohn.koomen@moffitt.org
dataset submitter
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Dataset FTP location
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