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Long-Noncoding RNA ANCR Activates the Hedgehog Signaling Pathway to Promote Basal Cell Carcinoma Progression by Binding to PTCH
PURPOSE: The long non-coding RNA (lncRNA) anti-differentiation noncoding RNA (ANCR) is closely related to the occurrence and development of various malignancies. However, its expression and potential role in basal cell carcinoma (BCC) have not been established. In this study, we characterized the ef...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9148612/ https://www.ncbi.nlm.nih.gov/pubmed/35642174 http://dx.doi.org/10.2147/CCID.S345371 |
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author | Wu, Hongxuan He, Pingxiu Xie, Dong Wang, Jianqiao Wan, Chuan |
author_facet | Wu, Hongxuan He, Pingxiu Xie, Dong Wang, Jianqiao Wan, Chuan |
author_sort | Wu, Hongxuan |
collection | PubMed |
description | PURPOSE: The long non-coding RNA (lncRNA) anti-differentiation noncoding RNA (ANCR) is closely related to the occurrence and development of various malignancies. However, its expression and potential role in basal cell carcinoma (BCC) have not been established. In this study, we characterized the effects of ANCR in BCC and its underlying mechanism. METHODS: The expression of ANCR in BCC tissues and cells was detected by qRT-PCR. Proliferation, invasion, migration and apoptosis of ANCR overexpressed or knock down TE354.T and A431 cells were examined by CCK8, transwell assay, wound healing assay and flow cytometry analysis, respectively. Western blot was performed to measure the expression of apoptosis-related proteins (BAX, BCL2 and Cleaved-caspase3), epithelial-mesenchymal transformation-related proteins (E-cadherin, N-cadherin, vimentin and β-catenin), and Hedgehog-pathway-related proteins (PTCH, GLI1 and SMO). RNA pull-down assay was used to analyze the relationship between ANCR and PTCH. The effect of ANCR on BCC growth in vivo was analyzed using xenograft model. TUNEL assay was used to determine the cell apoptosis. RESULTS: ANCR and Hedgehog pathway were more highly expressed in BCC tissues than in adjacent normal tissues. ANCR overexpression substantially promoted BCC cell proliferation, invasion, and migration, inhibited apoptosis, and up-regulated BCL2 and decreased the expression of BAX and Cleaved-caspase3 proteins. Additionally, the upregulation of N-cadherin, vimentin, β-catenin, PTCH, GLI1, and SMO expression, and downregulation of E-cadherin expression were observed after ANCR overexpression. Moreover, ANCR knockdown had the opposite effects. An RNA pull-down assay further revealed that ANCR is specifically bound to PTCH. In vivo experiments also showed that ANCR overexpression significantly increased tumor growth and decreased apoptosis, which was reversed by cyclopamine, a specific inhibitor of the Hedgehog signaling pathway. CONCLUSION: ANCR activates the Hedgehog signaling pathway by binding to PTCH, thereby promoting BCC progression; accordingly, ANCR could be a candidate therapeutic target in BCC. |
format | Online Article Text |
id | pubmed-9148612 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-91486122022-05-30 Long-Noncoding RNA ANCR Activates the Hedgehog Signaling Pathway to Promote Basal Cell Carcinoma Progression by Binding to PTCH Wu, Hongxuan He, Pingxiu Xie, Dong Wang, Jianqiao Wan, Chuan Clin Cosmet Investig Dermatol Original Research PURPOSE: The long non-coding RNA (lncRNA) anti-differentiation noncoding RNA (ANCR) is closely related to the occurrence and development of various malignancies. However, its expression and potential role in basal cell carcinoma (BCC) have not been established. In this study, we characterized the effects of ANCR in BCC and its underlying mechanism. METHODS: The expression of ANCR in BCC tissues and cells was detected by qRT-PCR. Proliferation, invasion, migration and apoptosis of ANCR overexpressed or knock down TE354.T and A431 cells were examined by CCK8, transwell assay, wound healing assay and flow cytometry analysis, respectively. Western blot was performed to measure the expression of apoptosis-related proteins (BAX, BCL2 and Cleaved-caspase3), epithelial-mesenchymal transformation-related proteins (E-cadherin, N-cadherin, vimentin and β-catenin), and Hedgehog-pathway-related proteins (PTCH, GLI1 and SMO). RNA pull-down assay was used to analyze the relationship between ANCR and PTCH. The effect of ANCR on BCC growth in vivo was analyzed using xenograft model. TUNEL assay was used to determine the cell apoptosis. RESULTS: ANCR and Hedgehog pathway were more highly expressed in BCC tissues than in adjacent normal tissues. ANCR overexpression substantially promoted BCC cell proliferation, invasion, and migration, inhibited apoptosis, and up-regulated BCL2 and decreased the expression of BAX and Cleaved-caspase3 proteins. Additionally, the upregulation of N-cadherin, vimentin, β-catenin, PTCH, GLI1, and SMO expression, and downregulation of E-cadherin expression were observed after ANCR overexpression. Moreover, ANCR knockdown had the opposite effects. An RNA pull-down assay further revealed that ANCR is specifically bound to PTCH. In vivo experiments also showed that ANCR overexpression significantly increased tumor growth and decreased apoptosis, which was reversed by cyclopamine, a specific inhibitor of the Hedgehog signaling pathway. CONCLUSION: ANCR activates the Hedgehog signaling pathway by binding to PTCH, thereby promoting BCC progression; accordingly, ANCR could be a candidate therapeutic target in BCC. Dove 2022-05-25 /pmc/articles/PMC9148612/ /pubmed/35642174 http://dx.doi.org/10.2147/CCID.S345371 Text en © 2022 Wu et al. https://creativecommons.org/licenses/by-nc/3.0/This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/ (https://creativecommons.org/licenses/by-nc/3.0/) ). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
spellingShingle | Original Research Wu, Hongxuan He, Pingxiu Xie, Dong Wang, Jianqiao Wan, Chuan Long-Noncoding RNA ANCR Activates the Hedgehog Signaling Pathway to Promote Basal Cell Carcinoma Progression by Binding to PTCH |
title | Long-Noncoding RNA ANCR Activates the Hedgehog Signaling Pathway to Promote Basal Cell Carcinoma Progression by Binding to PTCH |
title_full | Long-Noncoding RNA ANCR Activates the Hedgehog Signaling Pathway to Promote Basal Cell Carcinoma Progression by Binding to PTCH |
title_fullStr | Long-Noncoding RNA ANCR Activates the Hedgehog Signaling Pathway to Promote Basal Cell Carcinoma Progression by Binding to PTCH |
title_full_unstemmed | Long-Noncoding RNA ANCR Activates the Hedgehog Signaling Pathway to Promote Basal Cell Carcinoma Progression by Binding to PTCH |
title_short | Long-Noncoding RNA ANCR Activates the Hedgehog Signaling Pathway to Promote Basal Cell Carcinoma Progression by Binding to PTCH |
title_sort | long-noncoding rna ancr activates the hedgehog signaling pathway to promote basal cell carcinoma progression by binding to ptch |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9148612/ https://www.ncbi.nlm.nih.gov/pubmed/35642174 http://dx.doi.org/10.2147/CCID.S345371 |
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