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@ARTICLE{Chen:157750,
author = {I.-P. Chen and M. Bender and I. Spassova$^*$ and S. Henning
and L. Kubat$^*$ and K. Fan$^*$ and S. Degenhardt and M.
Mhamdi-Ghodbani and A. Sriram$^*$ and B. Volkmer and P.
Boukamp$^*$ and J. C. Becker$^*$ and R. Greinert},
title = {{UV}-type specific alteration of mi{RNA} expression and its
association with tumor progression and metastasis in {SCC}
cell lines.},
journal = {Journal of cancer research and clinical oncology},
volume = {146},
number = {12},
issn = {0171-5216},
address = {Berlin},
publisher = {Springer42162},
reportid = {DKFZ-2020-01787},
pages = {3215-3231},
year = {2020},
note = {2020 Dec;146(12):3215-3231},
abstract = {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.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.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.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.},
cin = {ED01 / A110},
ddc = {610},
cid = {I:(DE-He78)ED01-20160331 / I:(DE-He78)A110-20160331},
pnm = {311 - Signalling pathways, cell and tumor biology
(POF3-311)},
pid = {G:(DE-HGF)POF3-311},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:32865618},
doi = {10.1007/s00432-020-03358-9},
url = {https://inrepo02.dkfz.de/record/157750},
}