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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
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.
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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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