A cancer stem cell-like phenotype is associated with miR-10b expression in aggressive squamous cell carcinomas
| Autor: | Manuela Reisenberger, M. Wimmer, Stefan Hainzl, Julia Reichelt, Albert S. Mellick, Thomas Lettner, Johannes Proell, Christina Guttmann-Gruber, Mila Sajinovic, Eva M. Murauer, Verena Wally, Paul de Souza, Thomas Kocher, Michael Ablinger, R. Zauner, Johann W. Bauer, Norbert Niklas, Dirk Strunk, Josefina Piñón-Hofbauer |
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| Rok vydání: | 2020 |
| Předmět: |
Keratinocytes
Cell type Skin Neoplasms Primary Cell Culture Population Cell lcsh:Medicine Biology Biochemistry Metastasis Transcriptome 03 medical and health sciences 0302 clinical medicine Cancer stem cell Squamous cell carcinoma microRNA medicine Humans Neoplasm Invasiveness lcsh:QH573-671 Epidermolysis bullosa education Molecular Biology Cells Cultured 030304 developmental biology 0303 health sciences education.field_of_study lcsh:Cytology Research lcsh:R Cell Biology medicine.disease Epidermolysis Bullosa Dystrophica Gene Expression Regulation Neoplastic MicroRNAs medicine.anatomical_structure 030220 oncology & carcinogenesis Carcinoma Squamous Cell Neoplastic Stem Cells Cancer research miR-10b |
| Zdroj: | Cell Communication and Signaling : CCS Cell Communication and Signaling, Vol 18, Iss 1, Pp 1-15 (2020) |
| ISSN: | 1478-811X |
| DOI: | 10.1186/s12964-020-00550-9 |
| Popis: | Background Cutaneous squamous cell carcinomas (cSCC) are the primary cause of premature deaths in patients suffering from the rare skin-fragility disorder recessive dystrophic epidermolysis bullosa (RDEB), which is in marked contrast to the rarely metastasizing nature of these carcinomas in the general population. This remarkable difference is attributed to the frequent development of chronic wounds caused by impaired skin integrity. However, the specific molecular and cellular changes to malignancy, and whether there are common players in different types of aggressive cSCCs, remain relatively undefined. Methods MiRNA expression profiling was performed across various cell types isolated from skin and cSCCs. Microarray results were confirmed by qPCR and by an optimized in situ hybridization protocol. Functional impact of overexpression or knock-out of a dysregulated miRNA was assessed in migration and 3D-spheroid assays. Sample-matched transcriptome data was generated to support the identification of disease relevant miRNA targets. Results Several miRNAs were identified as dysregulated in cSCCs compared to control skin. These included the metastasis-linked miR-10b, which was significantly upregulated in primary cell cultures and in archival biopsies. At the functional level, overexpression of miR-10b conferred the stem cell-characteristic of 3D-spheroid formation capacity to keratinocytes. Analysis of miR-10b downstream effects identified a novel putative target of miR-10b, the actin- and tubulin cytoskeleton-associated protein DIAPH2. Conclusion The discovery that miR-10b mediates an aspect of cancer stemness – that of enhanced tumor cell adhesion, known to facilitate metastatic colonization – provides an important avenue for future development of novel therapies targeting this metastasis-linked miRNA. |
| Databáze: | OpenAIRE |
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