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Depletion of RIPK4 parallels higher malignancy potential in cutaneous squamous cell carcinoma

BACKGROUND: The RIPK4 (receptor-interacting protein kinase 4), a member of the RIPK family, acts as an important regulator of epidermal differentiation, cutaneous inflammation, and cutaneous wound repair. However, Until now, the role of RIPK4 in tumorigenesis remains elusive. There have been no stud...

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Autores principales: Xu, Jing, Wu, Dongping, Zhang, Bicheng, Pan, Chi, Guo, Yinglu, Wei, Qichun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: PeerJ Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8841032/
https://www.ncbi.nlm.nih.gov/pubmed/35186499
http://dx.doi.org/10.7717/peerj.12932
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author Xu, Jing
Wu, Dongping
Zhang, Bicheng
Pan, Chi
Guo, Yinglu
Wei, Qichun
author_facet Xu, Jing
Wu, Dongping
Zhang, Bicheng
Pan, Chi
Guo, Yinglu
Wei, Qichun
author_sort Xu, Jing
collection PubMed
description BACKGROUND: The RIPK4 (receptor-interacting protein kinase 4), a member of the RIPK family, acts as an important regulator of epidermal differentiation, cutaneous inflammation, and cutaneous wound repair. However, Until now, the role of RIPK4 in tumorigenesis remains elusive. There have been no studies exploring the effects of RIPK4 on the signaling pathway in cutaneous squamous cell carcinoma (SCC). It remains unknown whether RIPK4 expression, which can affect the degree of epidermal differentiation can also influence the radiosensitivity of skin SCC. It is urgent to fully elucidate the biological mechanism by which RIPK4 promotes carcinogenesis in skin SCC and determine whether RIPK4 expression levels predicts the sensitivity to radiotherapy in skin SCC. METHODS: Human skin SCC cell line, A431, was transfected with either small interfering RNAs (siRNAs) targeting RIPK4 (siR-RIPK4) or negative control siRNA (siR-NC). Western blotting was used to detect the expression of RIPK4 and Raf/MEK/ERK pathway-related proteins. The cells were irradiated using an X-ray irradiator at 6 MV with different radiation doses (0, 2, 6, and 10 Gy). Cell proliferation analysis, colony formation assay, transwell cell migration and invasion assay, cell cycle and apoptosis analysis were conducted to investigate the effect of RIPK4 silencing on skin SCC malignancy and radiosensitivity. RESULTS: RIPK4 protein expression was significantly decreased in the A431 cells transfected with siR-RIPK4, compared with the A431 cells transfected with siR-NC. RIPK4 silencing facilitated the proliferation, colony formation, migration, and invasion ability of A431 cell line, while cell cycle progression or cell apoptosis were not significantly influenced. In contrast with the previous literature, Raf/MEK/ERK pathway was not effected by RIPK4 knockdown in skin SCC. RIPK4 knockdown could not reverse the radiation resistance of A431 cells to irradiation in vitro. CONCLUSIONS: In general, although depletion of RIPK4 cannot reverse the radiation resistance of A431 cells in vitro, it parallels higher malignancy potential in cutaneous SCC. To our knowledge, this is the first report of the effects of RIPK4 expression on the Raf/MEK/ERK signaling pathway and radiosensitivity in cutaneous SCC. The better understanding of the molecular mechanism of RIPK4 in cutaneous SCC may provide a promising biomarker for skin SCC prognosis and treatment.
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spelling pubmed-88410322022-02-17 Depletion of RIPK4 parallels higher malignancy potential in cutaneous squamous cell carcinoma Xu, Jing Wu, Dongping Zhang, Bicheng Pan, Chi Guo, Yinglu Wei, Qichun PeerJ Biochemistry BACKGROUND: The RIPK4 (receptor-interacting protein kinase 4), a member of the RIPK family, acts as an important regulator of epidermal differentiation, cutaneous inflammation, and cutaneous wound repair. However, Until now, the role of RIPK4 in tumorigenesis remains elusive. There have been no studies exploring the effects of RIPK4 on the signaling pathway in cutaneous squamous cell carcinoma (SCC). It remains unknown whether RIPK4 expression, which can affect the degree of epidermal differentiation can also influence the radiosensitivity of skin SCC. It is urgent to fully elucidate the biological mechanism by which RIPK4 promotes carcinogenesis in skin SCC and determine whether RIPK4 expression levels predicts the sensitivity to radiotherapy in skin SCC. METHODS: Human skin SCC cell line, A431, was transfected with either small interfering RNAs (siRNAs) targeting RIPK4 (siR-RIPK4) or negative control siRNA (siR-NC). Western blotting was used to detect the expression of RIPK4 and Raf/MEK/ERK pathway-related proteins. The cells were irradiated using an X-ray irradiator at 6 MV with different radiation doses (0, 2, 6, and 10 Gy). Cell proliferation analysis, colony formation assay, transwell cell migration and invasion assay, cell cycle and apoptosis analysis were conducted to investigate the effect of RIPK4 silencing on skin SCC malignancy and radiosensitivity. RESULTS: RIPK4 protein expression was significantly decreased in the A431 cells transfected with siR-RIPK4, compared with the A431 cells transfected with siR-NC. RIPK4 silencing facilitated the proliferation, colony formation, migration, and invasion ability of A431 cell line, while cell cycle progression or cell apoptosis were not significantly influenced. In contrast with the previous literature, Raf/MEK/ERK pathway was not effected by RIPK4 knockdown in skin SCC. RIPK4 knockdown could not reverse the radiation resistance of A431 cells to irradiation in vitro. CONCLUSIONS: In general, although depletion of RIPK4 cannot reverse the radiation resistance of A431 cells in vitro, it parallels higher malignancy potential in cutaneous SCC. To our knowledge, this is the first report of the effects of RIPK4 expression on the Raf/MEK/ERK signaling pathway and radiosensitivity in cutaneous SCC. The better understanding of the molecular mechanism of RIPK4 in cutaneous SCC may provide a promising biomarker for skin SCC prognosis and treatment. PeerJ Inc. 2022-02-10 /pmc/articles/PMC8841032/ /pubmed/35186499 http://dx.doi.org/10.7717/peerj.12932 Text en © 2022 Xu et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited.
spellingShingle Biochemistry
Xu, Jing
Wu, Dongping
Zhang, Bicheng
Pan, Chi
Guo, Yinglu
Wei, Qichun
Depletion of RIPK4 parallels higher malignancy potential in cutaneous squamous cell carcinoma
title Depletion of RIPK4 parallels higher malignancy potential in cutaneous squamous cell carcinoma
title_full Depletion of RIPK4 parallels higher malignancy potential in cutaneous squamous cell carcinoma
title_fullStr Depletion of RIPK4 parallels higher malignancy potential in cutaneous squamous cell carcinoma
title_full_unstemmed Depletion of RIPK4 parallels higher malignancy potential in cutaneous squamous cell carcinoma
title_short Depletion of RIPK4 parallels higher malignancy potential in cutaneous squamous cell carcinoma
title_sort depletion of ripk4 parallels higher malignancy potential in cutaneous squamous cell carcinoma
topic Biochemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8841032/
https://www.ncbi.nlm.nih.gov/pubmed/35186499
http://dx.doi.org/10.7717/peerj.12932
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