Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA393708 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Skin carcinogenesis is known to be a multi-step process with several stages along its malignant evolution. We hypothesized that transformation of normal epidermis to cutaneous squamous cell carcinoma (cSCC) is causally linked to alterations in miRNA expression. For this end we decided to evaluate their alterations in the pathologic states ending in cSCC. Total RNA was extracted from FFPE biopsies of five stages along the malignant evolution of keratinocytes towards cSCC: Normal epidermis, severe solar elastosis (SE), actinic keratosis (KIN1-2), advanced actinic keratosis, (KIN3) and well differentiated cSCC. Next generation small RNA sequencing was performed. We found that 18 miRNAs are over expressed and 28 miRNAs are under expressed in cSCC compared to normal epidermis. miR-424, miR-320, miR- 222 and miR-15a showed the highest fold change among the over expressed miRNAs. And miR-100, miR-101 and miR-497 showed the highest fold change among the under expressed miRNAs. Heat map of hierarchical clustering analysis of significantly changed miRNAs and principle component analysis disclosed that the most prominent change in miRNAs expression occurred in the switch from “early” stages; normal epidermis, solar elastosis and early actinic keratosis to the “late” stages of epidermal carcinogenesis; late actinic keratosis and cSCC. We found several miRNAs with "stage specific" alterations while others display a clear “gradual”, either progressive increase or decrease in expression along the malignant evolution of keratinocytes. The observed alterations focused in miRNAs involved in the regulation of AKT/mTOR or in those involved in epithelial to mesenchymal transition. We chose to concentrate on the evaluation of the molecular role of miR- 497. We found that it induces reversion of epithelial to mesenchymal transition. We proved that SERPINE-1 is its biochemical target. The present study allows us to further study the pathways which are regulated by miRNAs along the malignant evolution of keratinocytes towards cSCC.
2017-12-31 | GSE101192 | GEO
Project description:Alterations of microRNAs throughout the malignant evolution of cutaneous squamous cell carcinoma
| PRJNA393854 | ENA
Project description:Cancer stem cells (CSCs) play a key role in tumour growth and metastasis. Although an expansion of CSC population was previously described in advanced cutaneous squamous cell carcinoma (SCC), it remains unknown whether CSC regulatory mechanisms also change through tumour progression to promote malignancy. Here, we generate mouse models of skin SCCs to study alterations in CSC regulation over progression. We found that features of CSCs change at late stage of progression, correlating with a switch from epithelial to mesenchymal tumour shape. beta-catenin and EGFR signalling are down-regulated, whereas autocrine FGFR1 and PDGFR alpha pathways are up-regulated in CSCs of advanced tumours. Inhibition of FGFR and PDGFR signalling repress malignant SCCs growth and metastasis, respectively. An enhanced epithelial-to-mesenchymal transition (EMT) program and over-expression of PDGFR alpha and FGFR1 are observed in malignant human skin SCCs, suggesting that these pathways are also induced over human SCC progression. Therefore, uncover signalling pathways controlling CSCs at specific stage of progression may improve the selection of more accurate targeted therapeutic strategies according to tumour stage, blocking SCC relapse and metastasis.
2016-01-08 | GSE59439 | GEO
Project description:Cancer stem cells (CSCs) play a key role in tumour growth and metastasis. Although an expansion of CSC population was previously described in advanced cutaneous squamous cell carcinoma (SCC), it remains unknown whether CSC regulatory mechanisms also change through tumour progression to promote malignancy. Here, we generate mouse models of skin SCCs to study alterations in CSC regulation over progression. We found that features of CSCs change at late stage of progression, correlating with a switch from epithelial to mesenchymal tumour shape. beta-catenin and EGFR signalling are down-regulated, whereas autocrine FGFR1 and PDGFR alpha pathways are up-regulated in CSCs of advanced tumours. Inhibition of FGFR and PDGFR signalling repress malignant SCCs growth and metastasis, respectively. An enhanced epithelial-to-mesenchymal transition (EMT) program and over-expression of PDGFR alpha and FGFR1 are observed in malignant human skin SCCs, suggesting that these pathways are also induced over human SCC progression. Therefore, uncover signalling pathways controlling CSCs at specific stage of progression may improve the selection of more accurate targeted therapeutic strategies according to tumour stage, blocking SCC relapse and metastasis. Mouse models of skin SCCs progression were first generated. For that, individual samples of spontaneous or DMBA-TPA induced skin SCCs generated in K14-HPV16 mice were orthotopically engrafted in immunodeficient mice and then serially transplanted, generating lineages in which the progression from WD-SCCs to PD-SCCs was observed. Then, tumour cells expressing CD34 and alpha 6-integrin, previously identified as cutaneous cancer stem cells, were isolated by flow cytometry-sorter from WD-SCCs and PD-SCCs of different tumour lineages. RNA extraction and hybridization on Affymetrix microarrays was carried out to compare whole gene profiling of these populations of CSCs.
2016-01-08 | E-GEOD-59439 | biostudies-arrayexpress
Project description:We found that miR-497 expression decrease in cSCC biopsies and cell lines compare to normal skin biopsies or normal keratinocytes cell. To understand in role lost expression of miR-497 might have in tumorigenesis of keratinocytes, we aimed to fine possible biochemical pathways and possible targets of miR-497 in cSCC. In order do so, we over expressed miR-497 in cSCC and used microarrays to fine global gene expression effected by miR-497.
2017-12-31 | GSE101096 | GEO
Project description:We focus on cancer-associated fibroblasts (CAFs) as an active component of the tumor microenvironment. The transcriptome profiling and analysis of CAFs isolated from breast cancer skin metastasis, cutaneous basal cell carcinoma and squamous cell carcinoma arising from oral cavity mucous membrane unravelled major gene candidates such as the IL-6, VEGF-A and MFGE8 that induced the expression of several markers associated with poor prognosis and epithelial-to-mesenchymal transition in co-cultivated EM-G3 breast cancer cells.
2023-10-02 | E-MTAB-12994 | biostudies-arrayexpress
Project description:Identification of the expression pattern of miRNAs at different stages of skin cancer progression in a panel of murine skin cancer cell lines miR-203 and miR-205 were differentially expressed in this panel, and were evaluated as biomarkers of prognosis in human cutaneous squamous cell carcinoma Three main tumor phenotypes: (i) Squamous non-malignant: Five non-malignant cell lines: three of them immortalized keratinocyte cell lines, and of them two papilloma cell lines. (ii) Three malignant squamous cell lines. (iii) Five malignant spindle cell lines. One replicate per array, except A5 that was done in duplicate as control
2015-08-11 | E-GEOD-71923 | biostudies-arrayexpress
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
Project description:The incidence of keratinocyte-derived skin cancer, cutaneous squamous cell carcinoma (cSCC) is increasing worldwide making it the second most common metastatic skin cancer. We used microarrays to characterize gene expression profile in normal human epidermal keratinocytes (NHEK) and cSCC cell lines. Total RNAs from normal human epidermal keratinocytes (n=5) and cSCC cell lines (n=8) were extracted. The samples were processed for Affymetrix 3´ IVT Express Kit according to manufacture’s protocol.
2015-08-27 | E-GEOD-66359 | biostudies-arrayexpress
Project description:The incidence of keratinocyte-derived skin cancer, cutaneous squamous cell carcinoma (cSCC) is increasing worldwide making it the second most common metastatic skin cancer. In this project we used SOLiD next generation sequencing to characterize gene expression profiles in normal human epidermal keratinocytes (NHEKs) and cSCC cell lines. Total RNAs from normal human epidermal keratinocytes (NHEKs) (n=4) and cSCC cell lines (n=8) were extracted. The samples were sequenced using SOLiD next generation sequencing.
2015-08-27 | E-GEOD-66412 | biostudies-arrayexpress