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

Jie Li,Li Zhou,Lin Lin,Yinguang Li,Hongye Jiang

doi:10.1007/s13258-021-01152-6

Abstract

BackgroundOvarian 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.ObjectiveThis article aims to investigate the role of FOSL2 in ovarian cancer development.MethodsFOSL2 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.ResultsThe 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.ConclusionsInhibition of FOSL2 promotes the apoptosis of OC cells by mediating the formation of an inflammasome.

Highlights

Ovarian cancer (OC) is a prevalent gynecological malignancy among women (Stewart and Lockwood 2019)
When compared with their control group, we found that overexpression of Fos-like antigen 2 (FOSL2) in A2780 cells significantly reduced cell apoptosis, whereas FOSL2 knockdown increased cell apoptosis (Fig. 3A–C)
All of these findings demonstrated that FOSL2 knockdown promotes cell apoptosis and inflammasomes activation

Summary

Introduction

Ovarian cancer (OC) is a prevalent gynecological malignancy among women (Stewart and Lockwood 2019). Fos-like antigen 2 (FOSL2) is a member of the activator protein-1 (AP1) transcription family that is widely expressed in various tissues and regulates the growth, development, reproduction, immune response, and other biological functions (Li et al 2018). Ovarian cancer is a common gynecological malignancy among female patients and poses a serious threat to women’s health. 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. 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). Conclusions Inhibition of FOSL2 promotes the apoptosis of OC cells by mediating the formation of an inflammasome

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Conclusion