Cargando…

SHARPIN regulates cell proliferation of cutaneous basal cell carcinoma via inactivation of the transcriptional factors GLI2 and c-JUN

SHANK-associated RH domain-interacting protein (SHARPIN) is a component of the linear ubiquitin chain assembly complex that can enhance the NF-κB and JNK signaling pathways, acting as a tumor-associated protein in a variety of cancer types. The present study investigated the role of SHARPIN in cutan...

Descripción completa

Detalles Bibliográficos
Autores principales: Yang, Yao, Liang, Yan-Hua, Zheng, Yan, Tang, Ling-Jie, Zhou, Si-Tong, Zhu, Jing-Na
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7057814/
https://www.ncbi.nlm.nih.gov/pubmed/32319607
http://dx.doi.org/10.3892/mmr.2020.10981
_version_ 1783503739619901440
author Yang, Yao
Liang, Yan-Hua
Zheng, Yan
Tang, Ling-Jie
Zhou, Si-Tong
Zhu, Jing-Na
author_facet Yang, Yao
Liang, Yan-Hua
Zheng, Yan
Tang, Ling-Jie
Zhou, Si-Tong
Zhu, Jing-Na
author_sort Yang, Yao
collection PubMed
description SHANK-associated RH domain-interacting protein (SHARPIN) is a component of the linear ubiquitin chain assembly complex that can enhance the NF-κB and JNK signaling pathways, acting as a tumor-associated protein in a variety of cancer types. The present study investigated the role of SHARPIN in cutaneous basal cell carcinoma (BCC). Human BCC (n=26) and normal skin (n=5) tissues, and BCC (TE354.T) and normal skin (HaCaT) cell lines were used to evaluate SHARPIN expression level using immunohistochemistry and western blotting, respectively. A lentivirus carrying SHARPIN-targeting or negative control short hairpin RNA was infected into TE354.T cells, and the infected stable cells were assayed to analyze tumor cell proliferation, cell cycle, apoptosis, migration and invasion by Cell Counting Kit-8 and 5-ethynyl-2′-deoxyuridine incorporation assays, flow cytometry and Transwell assays. Western blotting was performed to assess the protein expression levels of gene signaling in SHARPIN-silenced BCC cells. SHARPIN protein expression levels were downregulated or absent in BCC cancer nests and precancerous lesions compared with normal skin samples. In addition, SHARPIN expression levels were lower in TE354.T cells compared with HaCaT cells. SHARPIN shRNA enhanced tumor cell proliferation and the S phase of the cell cycle, whereas BCC cell apoptotic rates, and migratory and invasive abilities were not significantly altered. The expression levels of cyclin D1, cyclin-dependent kinase 4, phosphorylated-c-JUN and GLI family zinc finger 2 proteins were increased, whereas Patched 1 (PTCH1) and PTCH2 were decreased in the SHARPIN-shRNA-infected BCC cells. Therefore, the present results suggested that SHARPIN may act as a tumor suppressor during BCC development.
format Online
Article
Text
id pubmed-7057814
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher D.A. Spandidos
record_format MEDLINE/PubMed
spelling pubmed-70578142020-03-18 SHARPIN regulates cell proliferation of cutaneous basal cell carcinoma via inactivation of the transcriptional factors GLI2 and c-JUN Yang, Yao Liang, Yan-Hua Zheng, Yan Tang, Ling-Jie Zhou, Si-Tong Zhu, Jing-Na Mol Med Rep Articles SHANK-associated RH domain-interacting protein (SHARPIN) is a component of the linear ubiquitin chain assembly complex that can enhance the NF-κB and JNK signaling pathways, acting as a tumor-associated protein in a variety of cancer types. The present study investigated the role of SHARPIN in cutaneous basal cell carcinoma (BCC). Human BCC (n=26) and normal skin (n=5) tissues, and BCC (TE354.T) and normal skin (HaCaT) cell lines were used to evaluate SHARPIN expression level using immunohistochemistry and western blotting, respectively. A lentivirus carrying SHARPIN-targeting or negative control short hairpin RNA was infected into TE354.T cells, and the infected stable cells were assayed to analyze tumor cell proliferation, cell cycle, apoptosis, migration and invasion by Cell Counting Kit-8 and 5-ethynyl-2′-deoxyuridine incorporation assays, flow cytometry and Transwell assays. Western blotting was performed to assess the protein expression levels of gene signaling in SHARPIN-silenced BCC cells. SHARPIN protein expression levels were downregulated or absent in BCC cancer nests and precancerous lesions compared with normal skin samples. In addition, SHARPIN expression levels were lower in TE354.T cells compared with HaCaT cells. SHARPIN shRNA enhanced tumor cell proliferation and the S phase of the cell cycle, whereas BCC cell apoptotic rates, and migratory and invasive abilities were not significantly altered. The expression levels of cyclin D1, cyclin-dependent kinase 4, phosphorylated-c-JUN and GLI family zinc finger 2 proteins were increased, whereas Patched 1 (PTCH1) and PTCH2 were decreased in the SHARPIN-shRNA-infected BCC cells. Therefore, the present results suggested that SHARPIN may act as a tumor suppressor during BCC development. D.A. Spandidos 2020-04 2020-02-07 /pmc/articles/PMC7057814/ /pubmed/32319607 http://dx.doi.org/10.3892/mmr.2020.10981 Text en Copyright: © Yang et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Yang, Yao
Liang, Yan-Hua
Zheng, Yan
Tang, Ling-Jie
Zhou, Si-Tong
Zhu, Jing-Na
SHARPIN regulates cell proliferation of cutaneous basal cell carcinoma via inactivation of the transcriptional factors GLI2 and c-JUN
title SHARPIN regulates cell proliferation of cutaneous basal cell carcinoma via inactivation of the transcriptional factors GLI2 and c-JUN
title_full SHARPIN regulates cell proliferation of cutaneous basal cell carcinoma via inactivation of the transcriptional factors GLI2 and c-JUN
title_fullStr SHARPIN regulates cell proliferation of cutaneous basal cell carcinoma via inactivation of the transcriptional factors GLI2 and c-JUN
title_full_unstemmed SHARPIN regulates cell proliferation of cutaneous basal cell carcinoma via inactivation of the transcriptional factors GLI2 and c-JUN
title_short SHARPIN regulates cell proliferation of cutaneous basal cell carcinoma via inactivation of the transcriptional factors GLI2 and c-JUN
title_sort sharpin regulates cell proliferation of cutaneous basal cell carcinoma via inactivation of the transcriptional factors gli2 and c-jun
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7057814/
https://www.ncbi.nlm.nih.gov/pubmed/32319607
http://dx.doi.org/10.3892/mmr.2020.10981
work_keys_str_mv AT yangyao sharpinregulatescellproliferationofcutaneousbasalcellcarcinomaviainactivationofthetranscriptionalfactorsgli2andcjun
AT liangyanhua sharpinregulatescellproliferationofcutaneousbasalcellcarcinomaviainactivationofthetranscriptionalfactorsgli2andcjun
AT zhengyan sharpinregulatescellproliferationofcutaneousbasalcellcarcinomaviainactivationofthetranscriptionalfactorsgli2andcjun
AT tanglingjie sharpinregulatescellproliferationofcutaneousbasalcellcarcinomaviainactivationofthetranscriptionalfactorsgli2andcjun
AT zhousitong sharpinregulatescellproliferationofcutaneousbasalcellcarcinomaviainactivationofthetranscriptionalfactorsgli2andcjun
AT zhujingna sharpinregulatescellproliferationofcutaneousbasalcellcarcinomaviainactivationofthetranscriptionalfactorsgli2andcjun