UV-type specific alteration of miRNA expression and its association with tumor progression and metastasis in SCC cell li
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ORIGINAL ARTICLE – CANCER RESEARCH
UV‑type specific alteration of miRNA expression and its association with tumor progression and metastasis in SCC cell lines I‑Peng Chen1 · Marc Bender1 · Ivelina Spassova2 · Stefan Henning1 · Linda Kubat2 · Kaiji Fan2 · Sarah Degenhardt1 · Mouna Mhamdi‑Ghodbani1 · Ashwin Sriram2 · Beate Volkmer1 · Petra Boukamp3 · Jürgen C. Becker2 · Rüdiger Greinert1 Received: 18 December 2019 / Accepted: 18 August 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
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. Keywords Skin cancer · Cutaneous squamous cell carcinoma (cSCC) · cSCC cell lines · UV radiation · miRNAs · Metastasis
I-Peng Chen and Marc Bender contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00432-020-03358-9) contains supplementary material, which is available to authorized users. * Rüdiger Greinert [email protected] 1
Division of Molecular Cell Biology, Skin Cancer Center, Elbe Kliniken S
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