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SNX30 inhibits lung adenocarcinoma cell proliferation and induces cell ferroptosis through regulating SETDB1
Xinjie Fan1, Qichu Zhu2, Chengzhuo Du2
1Department of Respiratory and Critical Care Medicine, Datian County General Hospital, 180 Xueshan North Road, Datian County, 366100, China. fxj14391228@163.com.
Background:
Lung adenocarcinoma is the most common form of lung cancer and one of the most life-threatening malignant tumors. Ferroptosis is an iron-dependent regulatory cell death pathway that is crucial for tumor growth. SNX30 is a key regulatory factor in cardiac development; however, its regulatory mechanism and role in inducing ferroptosis in lung adenocarcinoma remain unclear.
Objective:
This study aimed to elucidate the functions and specific mechanisms of action of SNX30 in lung adenocarcinomas.
Methods:
SNX30 levels in lung adenocarcinoma cell lines (A549 and HCC827) were determined using reverse transcription quantitative real-time PCR (RT-qPCR) or western blotting. Cell proliferation and apoptosis were assessed by CCK8 and flow cytometry, respectively. The intracellular levels of total iron and Fe2+ were detected using Iron Assay Kits. Reactive oxygen species (ROS) levels were evaluated using a DCFH-DA probe and flow cytometry. Cysteine (Cys), glutathione (GSH), and glutathione peroxidase 4 (GPX4) levels were measured using detection assay kits. Other related markers, including Ptgs2, Chac1, SETDB1 cleaved-Caspase3, and Caspase3 were analyzed by RT-qPCR or western blotting.
Results:
SNX30 is downregulated in lung adenocarcinoma cell lines. SNX30-plasmid depressed lung adenocarcinoma cell proliferation, accelerated apoptosis, enhanced cleaved-Caspase3 expression and cleaved-Caspase3/Caspase3 ratio. Ferrostatin-1 significantly reversed the effects of the SNX30-plasmid on cell ferroptosis in lung adenocarcinoma, as confirmed by the reduced ROS levels, inhibited intracellular total iron and Fe2+ levels, decreased Ptgs2 and Chac1 expression, and increased Cys, GSH, and GPX4 release. We observed that the level of SETDB1 was lower in the SNX30-plasmid group than in the control-plasmid group, whereas the opposite results in ferrostatin-1 treated cells. SNX30 negatively regulates SETDB1 expression in lung adenocarcinoma cells. The upregulation of SETDB1 reversed the effects of the SNX30-plasmid on ferroptosis in lung adenocarcinoma cells.
Conclusion:
SNX30 inhibits lung adenocarcinoma cell proliferation and induces ferroptosis by regulating SETDB1 expression.
Insights
SNX30, a protein, inhibits lung adenocarcinoma cell growth and triggers ferroptosis (iron-dependent cell death). It achieves this by downregulating SETDB1, a key factor in tumor progression. This discovery offers new therapeutic targets for lung cancer.
Area of Science:
- Oncology
- Cell Biology
- Biochemistry
Background:
- Lung adenocarcinoma is a prevalent and lethal cancer.
- Ferroptosis, an iron-dependent cell death, plays a role in tumor development.
- The function of SNX30 in lung adenocarcinoma and ferroptosis is not well understood.
Purpose of the Study:
- To investigate the role and mechanism of SNX30 in lung adenocarcinoma.
- To determine if SNX30 influences ferroptosis in lung cancer cells.
Main Methods:
- Assessed SNX30 expression in lung adenocarcinoma cell lines using RT-qPCR and Western blotting.
- Measured cell proliferation, apoptosis, iron levels, reactive oxygen species (ROS), and key ferroptosis markers (Cys, GSH, GPX4).
- Analyzed the expression of SETDB1, Ptgs2, Chac1, and Caspase3.
Main Results:
- SNX30 was found to be downregulated in lung adenocarcinoma cells.
- SNX30 suppressed cell proliferation, promoted apoptosis, and induced ferroptosis.
- SNX30 negatively regulated SETDB1 expression, and SETDB1 upregulation reversed SNX30's effects on ferroptosis.
Conclusions:
- SNX30 inhibits lung adenocarcinoma cell proliferation.
- SNX30 induces ferroptosis by regulating SETDB1 expression.
- SNX30 represents a potential therapeutic target for lung adenocarcinoma.
