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Sohlh2 Inhibits the Malignant Progression of Renal Cell Carcinoma by Upregulating Klotho via DNMT3a

BACKGROUND: Renal cell carcinoma is the most common malignant tumor of the kidney. The 5-year survival of renal cell carcinoma with distant metastasis is very low. Sohlh2 is a newly discovered tumor suppressor gene playing inhibitory roles in a variety of tumors, but its role in renal cell carcinoma...

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Autores principales: Liu, Yang, Cui, Weiwei, Zhang, Ruihong, Zhi, Sujuan, Liu, Lanlan, Liu, Xuyue, Feng, Xiaoning, Chen, Yanru, Zhang, Xiaoli, Hao, Jing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8807643/
https://www.ncbi.nlm.nih.gov/pubmed/35127476
http://dx.doi.org/10.3389/fonc.2021.769493
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author Liu, Yang
Cui, Weiwei
Zhang, Ruihong
Zhi, Sujuan
Liu, Lanlan
Liu, Xuyue
Feng, Xiaoning
Chen, Yanru
Zhang, Xiaoli
Hao, Jing
author_facet Liu, Yang
Cui, Weiwei
Zhang, Ruihong
Zhi, Sujuan
Liu, Lanlan
Liu, Xuyue
Feng, Xiaoning
Chen, Yanru
Zhang, Xiaoli
Hao, Jing
author_sort Liu, Yang
collection PubMed
description BACKGROUND: Renal cell carcinoma is the most common malignant tumor of the kidney. The 5-year survival of renal cell carcinoma with distant metastasis is very low. Sohlh2 is a newly discovered tumor suppressor gene playing inhibitory roles in a variety of tumors, but its role in renal cell carcinoma has not been reported. METHODS: To clarify the role of Sohlh2 in the occurrence and development of renal cell carcinoma, we constructed stably transfected human renal cell carcinoma cell lines with Sohlh2 overexpression and Sohlh2 knockdown, separately. First, we studied the effects of Sohlh2 on proliferation, migration, invasion, and epithelial–mesenchymal transition (EMT) of renal cell carcinoma cells in vitro and in vivo. Then, we detected whether Sohlh2 functions through DNMT3a/Klotho using Western blotting, qPCR, and Cell Counting Kit-8 (CCK-8) assay. Finally, we collected 40 resected renal cell carcinoma samples to study the relevance between Sohlh2, DNMT3a, and Klotho by immunohistochemistry. RESULTS: Our results showed that Sohlh2 was downregulated in renal cell carcinoma, and its expression level was negatively correlated with tumor staging. Both in vitro and in vivo experiments confirmed that Sohlh2 overexpression inhibited the proliferation, migration, invasion, metastasis, and EMT of renal cell carcinoma. Sohlh2 functions through demethylation of Klotho by downregulating the expression of DNA methyltransferase of DNMT3a. In renal cell carcinoma, Sohlh2 was positively correlated with Klotho and negatively correlated with DNMT3a. CONCLUSION: Sohlh2 functions as a tumor suppressor gene in renal cell carcinoma by demethylation of Klotho via DNMT3a. Sohlh2 correlated with Klotho positively and with DNMT3a negatively in renal cell carcinoma. Our study suggests that Sohlh2 and DNMT3a/Klotho can be used as potential targets for the clinical treatment of renal cell carcinoma.
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spelling pubmed-88076432022-02-03 Sohlh2 Inhibits the Malignant Progression of Renal Cell Carcinoma by Upregulating Klotho via DNMT3a Liu, Yang Cui, Weiwei Zhang, Ruihong Zhi, Sujuan Liu, Lanlan Liu, Xuyue Feng, Xiaoning Chen, Yanru Zhang, Xiaoli Hao, Jing Front Oncol Oncology BACKGROUND: Renal cell carcinoma is the most common malignant tumor of the kidney. The 5-year survival of renal cell carcinoma with distant metastasis is very low. Sohlh2 is a newly discovered tumor suppressor gene playing inhibitory roles in a variety of tumors, but its role in renal cell carcinoma has not been reported. METHODS: To clarify the role of Sohlh2 in the occurrence and development of renal cell carcinoma, we constructed stably transfected human renal cell carcinoma cell lines with Sohlh2 overexpression and Sohlh2 knockdown, separately. First, we studied the effects of Sohlh2 on proliferation, migration, invasion, and epithelial–mesenchymal transition (EMT) of renal cell carcinoma cells in vitro and in vivo. Then, we detected whether Sohlh2 functions through DNMT3a/Klotho using Western blotting, qPCR, and Cell Counting Kit-8 (CCK-8) assay. Finally, we collected 40 resected renal cell carcinoma samples to study the relevance between Sohlh2, DNMT3a, and Klotho by immunohistochemistry. RESULTS: Our results showed that Sohlh2 was downregulated in renal cell carcinoma, and its expression level was negatively correlated with tumor staging. Both in vitro and in vivo experiments confirmed that Sohlh2 overexpression inhibited the proliferation, migration, invasion, metastasis, and EMT of renal cell carcinoma. Sohlh2 functions through demethylation of Klotho by downregulating the expression of DNA methyltransferase of DNMT3a. In renal cell carcinoma, Sohlh2 was positively correlated with Klotho and negatively correlated with DNMT3a. CONCLUSION: Sohlh2 functions as a tumor suppressor gene in renal cell carcinoma by demethylation of Klotho via DNMT3a. Sohlh2 correlated with Klotho positively and with DNMT3a negatively in renal cell carcinoma. Our study suggests that Sohlh2 and DNMT3a/Klotho can be used as potential targets for the clinical treatment of renal cell carcinoma. Frontiers Media S.A. 2022-01-19 /pmc/articles/PMC8807643/ /pubmed/35127476 http://dx.doi.org/10.3389/fonc.2021.769493 Text en Copyright © 2022 Liu, Cui, Zhang, Zhi, Liu, Liu, Feng, Chen, Zhang and Hao https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Liu, Yang
Cui, Weiwei
Zhang, Ruihong
Zhi, Sujuan
Liu, Lanlan
Liu, Xuyue
Feng, Xiaoning
Chen, Yanru
Zhang, Xiaoli
Hao, Jing
Sohlh2 Inhibits the Malignant Progression of Renal Cell Carcinoma by Upregulating Klotho via DNMT3a
title Sohlh2 Inhibits the Malignant Progression of Renal Cell Carcinoma by Upregulating Klotho via DNMT3a
title_full Sohlh2 Inhibits the Malignant Progression of Renal Cell Carcinoma by Upregulating Klotho via DNMT3a
title_fullStr Sohlh2 Inhibits the Malignant Progression of Renal Cell Carcinoma by Upregulating Klotho via DNMT3a
title_full_unstemmed Sohlh2 Inhibits the Malignant Progression of Renal Cell Carcinoma by Upregulating Klotho via DNMT3a
title_short Sohlh2 Inhibits the Malignant Progression of Renal Cell Carcinoma by Upregulating Klotho via DNMT3a
title_sort sohlh2 inhibits the malignant progression of renal cell carcinoma by upregulating klotho via dnmt3a
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8807643/
https://www.ncbi.nlm.nih.gov/pubmed/35127476
http://dx.doi.org/10.3389/fonc.2021.769493
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