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Published in: Journal of Cancer Research and Clinical Oncology 12/2020

01-12-2020 | Metastasis | Original Article – Cancer Research

UV-type specific alteration of miRNA expression and its association with tumor progression and metastasis in SCC cell lines

Authors: I-Peng Chen, Marc Bender, Ivelina Spassova, Stefan Henning, Linda Kubat, Kaiji Fan, Sarah Degenhardt, Mouna Mhamdi-Ghodbani, Ashwin Sriram, Beate Volkmer, Petra Boukamp, Jürgen C. Becker, Rüdiger Greinert

Published in: Journal of Cancer Research and Clinical Oncology | Issue 12/2020

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Abstract

Purpose

UV exposure is the main risk factor for development of cutaneous squamous cell carcinoma (cSCC). While early detection greatly improves cSCC prognosis, locally advanced or metastatic cSCC has a severely impaired prognosis. Notably, the mechanisms of progression to metastatic cSCC are not well understood. We hypothesized that UV exposure of already transformed epithelial cSCC cells further induces changes which might be involved in the progression to metastatic cSCCs and that UV-inducible microRNAs (miRNAs) might play an important role.

Methods

Thus, we analyzed the impact of UV radiation of different quality (UVA, UVB, UVA + UVB) on the miRNA expression pattern in established cell lines generated from primary and metastatic cSCCs (Met-1, Met-4) using the NanoString nCounter platform.

Results

This analysis revealed that the expression pattern of miRNAs depends on both the cell line used per se and on the quality of UV radiation. Comparison of UV-induced miRNAs in cSCC cell lines established from a primary tumor (Met-1) and the respective (un-irradiated) metastasis (Met-4) suggest that miR-7-5p, miR-29a-3p and miR-183-5p are involved in a UV-driven pathway of progression to metastasis. This notion is supported by the fact that these three miRNAs build up a network of 81 potential target genes involved e.g. in UVA/UVB-induced MAPK signaling and regulation of the epithelial–mesenchymal transition. As an example, PTEN, a target of UV-upregulated miRNAs (miR-29a-3p, miR-183-5p), could be shown to be down-regulated in response to UV radiation. We further identified CNOT8, the transcription complex subunit 8 of the CCR4-NOT complex, a deadenylase removing the poly(A) tail from miRNA-destabilized mRNAs, in the center of this network, targeted by all three miRNAs.

Conclusion

In summary, our results demonstrate that UV radiation induces an miRNA expression pattern in primary SCC cell line partly resembling those of metastatic cell line, thus suggesting that UV radiation impacts SCC progression beyond initiation.
Appendix
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Literature
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Metadata
Title
UV-type specific alteration of miRNA expression and its association with tumor progression and metastasis in SCC cell lines
Authors
I-Peng Chen
Marc Bender
Ivelina Spassova
Stefan Henning
Linda Kubat
Kaiji Fan
Sarah Degenhardt
Mouna Mhamdi-Ghodbani
Ashwin Sriram
Beate Volkmer
Petra Boukamp
Jürgen C. Becker
Rüdiger Greinert
Publication date
01-12-2020
Publisher
Springer Berlin Heidelberg
Published in
Journal of Cancer Research and Clinical Oncology / Issue 12/2020
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-020-03358-9

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