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HSPA5 regulates proliferation and apoptosis of cervical cancer cells through inhibiting ferroptosis

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2023 11
Page:
1996-2002
Research Field:
Publishing date:

Info

Title:
HSPA5 regulates proliferation and apoptosis of cervical cancer cells through inhibiting ferroptosis
Author(s):
HU Yaorui1; 2; YANG Liu3; PEI Yao2; HU Wei2; YANG Chunhua2; ZHANG Luping1
1.Institute of Neurobiology,Binzhou Medical University,Shandong Yantai 264000,China;2.Shandong Technology Innovation Center of Molecular targeting and Intelligent Diagnosis and Treatment,Binzhou Medical University,Shandong Yantai 264000,China;3.Department of Paediatrics,Jinan Central Hospital,Shandong Jinan 250013,China.
Keywords:
HSPA5; ferroptosis; cervical cancer; proliferation; apoptosis
PACS:
R737.33
DOI:
10.3969/j.issn.1672-4992.2023.11.005
Abstract:
Objective:To investigate the effects of HSPA5 on the proliferation and apoptosis of cervical cancer cells through ferroptosis.Methods:Quantitative Real-time PCR (qRT-PCR) and Western Blot (WB) were used to detect the expression of HSPA5 and GPX4 in cervical cancer and paracancerous tissues.The relationship between HSPA5 and overall survival rate for all patients with cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) was analyzed based on TCGA database.Human cervical cancer HeLa and SiHa cell lines were cultured in vitro,and infected with shHSPA5 or shCtrl lentivirus to construct a stable strain of HSPA5 knockdown.qRT-PCR and WB were used to detected the expression of ferroptosis-related protein GPX4 after HSPA5 knockdown.CCK-8 and EdU cell proliferation assay，lactate dehydrogenase (LDH) assay，glutathione (GSH) kit，malondialdehyde (MDA) kit and flow cytometry analysis were used to determined cell proliferation，LDH，GSH and MDA content，cell apoptosis and reactive oxygen species (ROS) with ferroptosis inhibitor Ferrostatin-1 (Fer-1) or ferroptosis activator Erastin treatment.Results:Compared with paracancerous tissue,the expression of HSPA5 and GPX4 in cervical cancer tissue was significantly higher.High HSPA5 level was consistent with poor prognosis.Knockdown of HSPA5 in HeLa and SiHa cells inhibited cell proliferation and increased cell apoptosis,meanwhile increased the levels of ROS,MDA and LDH in cells.Both mRNA and protein expression levels of GPX4 were reduced after HSPA5 knockdown,and the content of GSH in cells decreased.Treatment of Fer-1,an ferroptosis inhibitor,reversed the increased of ROS and LDH content induced by HSPA5 knockdown and inhibited cell apoptosis.In contrast,treatment of Erastin,an ferroptosis inducer,increased cell apoptosis and inhibitd cell proliferation cooperatively with HSPA5 knockdown.Conclusion:The results indicate that HSPA5 level is upregulated in cervical cancer tissues and HSPA5 knockdown inhibits proliferation and promotes apoptosis of cervical cancer cells through activating ferroptosis.

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Memo

Memo:
山东省自然科学基金资助项目（编号：ZR2021MH141）
Last Update: 2023-04-28