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Inhibition of NEK7 Suppressed Hepatocellular Carcinoma Progression by Mediating Cancer Cell Pyroptosis
NIMA-related kinase 7 (NEK7) is a serine/threonine kinase involved in cell cycle progression via mitotic spindle formation and cytokinesis. It has been related to multiple cancers, including breast cancer, hepatocellular cancer, lung cancer, and colorectal cancer. Moreover, NEK7 regulated the NLRP3...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8866693/ https://www.ncbi.nlm.nih.gov/pubmed/35223495 http://dx.doi.org/10.3389/fonc.2022.812655 |
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author | Yan, Zilong Da, Qingen Li, Zhangfu Lin, Qirui Yi, Jing Su, Yanze Yu, Guanyin Ren, Qingqi Liu, Xu Lin, Zewei Qu, Jianhua Yin, Weihua Liu, Jikui |
author_facet | Yan, Zilong Da, Qingen Li, Zhangfu Lin, Qirui Yi, Jing Su, Yanze Yu, Guanyin Ren, Qingqi Liu, Xu Lin, Zewei Qu, Jianhua Yin, Weihua Liu, Jikui |
author_sort | Yan, Zilong |
collection | PubMed |
description | NIMA-related kinase 7 (NEK7) is a serine/threonine kinase involved in cell cycle progression via mitotic spindle formation and cytokinesis. It has been related to multiple cancers, including breast cancer, hepatocellular cancer, lung cancer, and colorectal cancer. Moreover, NEK7 regulated the NLRP3 inflammasome to activate Caspase-1, resulting in cell pyroptosis. In the present study, we investigated whether NEK7 is involved in cell pyroptosis of hepatocellular carcinoma (HCC). Interestingly, we found that NEK7 was significantly related to expression of pyroptosis marker GSDMD in HCC. We found that NEK7 expression was significantly correlated with GSDMD expression in bioinformatics analysis, and NEK7 expression was significantly co-expressed with GSDMD in our HCC specimens. Cell viability, migration, and invasion capacity of HCC cell lines were inhibited, and the tumor growth in the xenograft mouse model was also suppressed following knockdown of NEK7 expression. Mechanistic studies revealed that knockdown of NEK7 in HCC cells significantly upregulated the expression of pyroptosis markers such as NLRP3, Caspase-1, and GSDMD. Coculture of HCC cells stimulated hepatic stellate cell activation by increasing p-ERK1/2 and α-SMA. Knockdown of NEK7 impaired the stimulation of HCC cells. Therefore, downregulation of NEK7 inhibited cancer–stromal interaction by triggering cancer cell pyroptosis. Taken together, this study highlights the functional role of NEK7-regulated pyroptosis in tumor progression and cancer–stromal interaction of HCC, suggesting NEK7 as a potential target for a new therapeutic strategy of HCC treatment. |
format | Online Article Text |
id | pubmed-8866693 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-88666932022-02-25 Inhibition of NEK7 Suppressed Hepatocellular Carcinoma Progression by Mediating Cancer Cell Pyroptosis Yan, Zilong Da, Qingen Li, Zhangfu Lin, Qirui Yi, Jing Su, Yanze Yu, Guanyin Ren, Qingqi Liu, Xu Lin, Zewei Qu, Jianhua Yin, Weihua Liu, Jikui Front Oncol Oncology NIMA-related kinase 7 (NEK7) is a serine/threonine kinase involved in cell cycle progression via mitotic spindle formation and cytokinesis. It has been related to multiple cancers, including breast cancer, hepatocellular cancer, lung cancer, and colorectal cancer. Moreover, NEK7 regulated the NLRP3 inflammasome to activate Caspase-1, resulting in cell pyroptosis. In the present study, we investigated whether NEK7 is involved in cell pyroptosis of hepatocellular carcinoma (HCC). Interestingly, we found that NEK7 was significantly related to expression of pyroptosis marker GSDMD in HCC. We found that NEK7 expression was significantly correlated with GSDMD expression in bioinformatics analysis, and NEK7 expression was significantly co-expressed with GSDMD in our HCC specimens. Cell viability, migration, and invasion capacity of HCC cell lines were inhibited, and the tumor growth in the xenograft mouse model was also suppressed following knockdown of NEK7 expression. Mechanistic studies revealed that knockdown of NEK7 in HCC cells significantly upregulated the expression of pyroptosis markers such as NLRP3, Caspase-1, and GSDMD. Coculture of HCC cells stimulated hepatic stellate cell activation by increasing p-ERK1/2 and α-SMA. Knockdown of NEK7 impaired the stimulation of HCC cells. Therefore, downregulation of NEK7 inhibited cancer–stromal interaction by triggering cancer cell pyroptosis. Taken together, this study highlights the functional role of NEK7-regulated pyroptosis in tumor progression and cancer–stromal interaction of HCC, suggesting NEK7 as a potential target for a new therapeutic strategy of HCC treatment. Frontiers Media S.A. 2022-02-10 /pmc/articles/PMC8866693/ /pubmed/35223495 http://dx.doi.org/10.3389/fonc.2022.812655 Text en Copyright © 2022 Yan, Da, Li, Lin, Yi, Su, Yu, Ren, Liu, Lin, Qu, Yin and Liu 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 Yan, Zilong Da, Qingen Li, Zhangfu Lin, Qirui Yi, Jing Su, Yanze Yu, Guanyin Ren, Qingqi Liu, Xu Lin, Zewei Qu, Jianhua Yin, Weihua Liu, Jikui Inhibition of NEK7 Suppressed Hepatocellular Carcinoma Progression by Mediating Cancer Cell Pyroptosis |
title | Inhibition of NEK7 Suppressed Hepatocellular Carcinoma Progression by Mediating Cancer Cell Pyroptosis |
title_full | Inhibition of NEK7 Suppressed Hepatocellular Carcinoma Progression by Mediating Cancer Cell Pyroptosis |
title_fullStr | Inhibition of NEK7 Suppressed Hepatocellular Carcinoma Progression by Mediating Cancer Cell Pyroptosis |
title_full_unstemmed | Inhibition of NEK7 Suppressed Hepatocellular Carcinoma Progression by Mediating Cancer Cell Pyroptosis |
title_short | Inhibition of NEK7 Suppressed Hepatocellular Carcinoma Progression by Mediating Cancer Cell Pyroptosis |
title_sort | inhibition of nek7 suppressed hepatocellular carcinoma progression by mediating cancer cell pyroptosis |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8866693/ https://www.ncbi.nlm.nih.gov/pubmed/35223495 http://dx.doi.org/10.3389/fonc.2022.812655 |
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