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Inhibition of FOSL2 aggravates the apoptosis of ovarian cancer cells by promoting the formation of inflammasomes

BACKGROUND: Ovarian cancer is a common gynecological malignancy among female patients and poses a serious threat to women’s health. Although it has been established that Fos-like antigen 2 (FOSL2) is linked to ovarian cancer (OC), its exact role in the development of OC remains unknown. OBJECTIVE: T...

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Autores principales: Li, Jie, Zhou, Li, Jiang, Hongye, Lin, Lin, Li, Yinguang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Singapore 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8727396/
https://www.ncbi.nlm.nih.gov/pubmed/34773569
http://dx.doi.org/10.1007/s13258-021-01152-6
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author Li, Jie
Zhou, Li
Jiang, Hongye
Lin, Lin
Li, Yinguang
author_facet Li, Jie
Zhou, Li
Jiang, Hongye
Lin, Lin
Li, Yinguang
author_sort Li, Jie
collection PubMed
description BACKGROUND: Ovarian cancer is a common gynecological malignancy among female patients and poses a serious threat to women’s health. Although it has been established that Fos-like antigen 2 (FOSL2) is linked to ovarian cancer (OC), its exact role in the development of OC remains unknown. OBJECTIVE: This article aims to investigate the role of FOSL2 in ovarian cancer development. METHODS: FOSL2 expression in ovarian carcinoma and adjacent tissues was assessed using real-time fluorescent quantitative PCR and western blot. We constructed OE/sh-FOSL2 plasmids and Caspase-1 specific inhibitors (Yvad-CMK) and transfected A 2780 cells with them to identify the relevant cell functions. Furthermore, we used western blot assay to determine the changes in expression of apoptosis-associated speck-like protein containing a CARD (ASC), cysteine aspartate-specific proteasezymogen procaspase 1 (pro-caspase-1), cysteinyl aspartate-specific proteinase-1 (caspase-1), interleukin-1β precursor (pro-IL-1β), interleukin-1β (IL-1β), interleukin-18 precursor (pro-IL-18), and interleukin-18 (IL-18). In addition, we measured the concentration of IL-1β and IL-18 using an enzyme-linked immunosorbent assay (ELISA). Moreover, Tthe level of lactate dehydrogenase (LDH) in the cell supernatant was measured by LDH release assay kit. RESULTS: The expression of FOSL2 was significantly higher compared with the surrounding tissues. The proliferation, migration, and invasion of A2780 cells were enhanced after transfection with OE-FOSL2 plasmids; however, the cell apoptosis was significantly decreased. When FOSL2 was overexpressed, the inflammasome-associated proteins such as ASC, caspase-1, IL-1β, and IL-18 were downregulated. Furthermore, FOSL2 induced apoptosis and activated the production of inflammasomes in A2780 cells. Co-therapy with Yvad-CMK and substantially inhibited apoptosis and activation of inflammasomes. CONCLUSIONS: Inhibition of FOSL2 promotes the apoptosis of OC cells by mediating the formation of an inflammasome.
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spelling pubmed-87273962022-01-18 Inhibition of FOSL2 aggravates the apoptosis of ovarian cancer cells by promoting the formation of inflammasomes Li, Jie Zhou, Li Jiang, Hongye Lin, Lin Li, Yinguang Genes Genomics Research Article BACKGROUND: Ovarian cancer is a common gynecological malignancy among female patients and poses a serious threat to women’s health. Although it has been established that Fos-like antigen 2 (FOSL2) is linked to ovarian cancer (OC), its exact role in the development of OC remains unknown. OBJECTIVE: This article aims to investigate the role of FOSL2 in ovarian cancer development. METHODS: FOSL2 expression in ovarian carcinoma and adjacent tissues was assessed using real-time fluorescent quantitative PCR and western blot. We constructed OE/sh-FOSL2 plasmids and Caspase-1 specific inhibitors (Yvad-CMK) and transfected A 2780 cells with them to identify the relevant cell functions. Furthermore, we used western blot assay to determine the changes in expression of apoptosis-associated speck-like protein containing a CARD (ASC), cysteine aspartate-specific proteasezymogen procaspase 1 (pro-caspase-1), cysteinyl aspartate-specific proteinase-1 (caspase-1), interleukin-1β precursor (pro-IL-1β), interleukin-1β (IL-1β), interleukin-18 precursor (pro-IL-18), and interleukin-18 (IL-18). In addition, we measured the concentration of IL-1β and IL-18 using an enzyme-linked immunosorbent assay (ELISA). Moreover, Tthe level of lactate dehydrogenase (LDH) in the cell supernatant was measured by LDH release assay kit. RESULTS: The expression of FOSL2 was significantly higher compared with the surrounding tissues. The proliferation, migration, and invasion of A2780 cells were enhanced after transfection with OE-FOSL2 plasmids; however, the cell apoptosis was significantly decreased. When FOSL2 was overexpressed, the inflammasome-associated proteins such as ASC, caspase-1, IL-1β, and IL-18 were downregulated. Furthermore, FOSL2 induced apoptosis and activated the production of inflammasomes in A2780 cells. Co-therapy with Yvad-CMK and substantially inhibited apoptosis and activation of inflammasomes. CONCLUSIONS: Inhibition of FOSL2 promotes the apoptosis of OC cells by mediating the formation of an inflammasome. Springer Singapore 2021-11-13 2022 /pmc/articles/PMC8727396/ /pubmed/34773569 http://dx.doi.org/10.1007/s13258-021-01152-6 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Li, Jie
Zhou, Li
Jiang, Hongye
Lin, Lin
Li, Yinguang
Inhibition of FOSL2 aggravates the apoptosis of ovarian cancer cells by promoting the formation of inflammasomes
title Inhibition of FOSL2 aggravates the apoptosis of ovarian cancer cells by promoting the formation of inflammasomes
title_full Inhibition of FOSL2 aggravates the apoptosis of ovarian cancer cells by promoting the formation of inflammasomes
title_fullStr Inhibition of FOSL2 aggravates the apoptosis of ovarian cancer cells by promoting the formation of inflammasomes
title_full_unstemmed Inhibition of FOSL2 aggravates the apoptosis of ovarian cancer cells by promoting the formation of inflammasomes
title_short Inhibition of FOSL2 aggravates the apoptosis of ovarian cancer cells by promoting the formation of inflammasomes
title_sort inhibition of fosl2 aggravates the apoptosis of ovarian cancer cells by promoting the formation of inflammasomes
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8727396/
https://www.ncbi.nlm.nih.gov/pubmed/34773569
http://dx.doi.org/10.1007/s13258-021-01152-6
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