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Knockdown CYP2S1 inhibits lung cancer cells proliferation and migration
Huan Guo1,2,1, Baozhen Zeng3,1, Liqiong Wang1
1Department of Oncology, Yan'an Hospital, Kunming Medical University, Kunming, Yunnan, China.
Background:
The incidence of lung cancer in Yunnan area ranks firstly in the world and underlying molecular mechanisms of lung cancer in Yunnan region are still unclear. We screened a novel potential oncogene CYP2S1 used mRNA microassay and bioinformation database. The function of CYP2S1 in lung cancer has not been reported.
Objective:
To investigate the functions of CYP2S1 in lung cancer.
Methods:
Immunohistochemistry and Real-time PCR were used to verify the expression of CYP2S1. Colony formation and Transwell assays were used to determine cell proliferation, invasion and migration. Xenograft assays were used to detected cell growth in vivo.
Results:
CYP2S1 is significantly up-regulated in lung cancer tissues and cells. Knockdown CYP2S1 in lung cancer cells resulted in decrease cell proliferation, invasion and migration in vitro. Animal experiments showed downregulation of CYP2S1 inhibited lung cancer cell growth in vivo. GSEA analysis suggested that CYP2S1 played functions by regulating E2F targets and G2M checkpoint pathway which involved in cell cycle. Kaplan-Meier analysis indicated that patients with high CYP2S1 had markedly shorter event overall survival (OS) time.
Conclusions:
Our data demonstrate that CYP2S1 exerts tumor suppressor function in lung cancer. The high expression of CYP2S1 is an unfavorable prognostic marker for patient survival.
Insights
CYP2S1 is significantly upregulated in lung cancer, suppressing tumor growth and progression. High CYP2S1 expression indicates poor prognosis, highlighting its role as a potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Genetics
Background:
- Lung cancer incidence is highest globally in the Yunnan region, with unclear molecular drivers.
- CYP2S1 identified as a novel potential oncogene via mRNA microassay and bioinformatics.
- The specific role of CYP2S1 in lung cancer pathogenesis remains unexplored.
Purpose of the Study:
- To elucidate the functional role of CYP2S1 in the development and progression of lung cancer.
- To investigate CYP2S1 as a potential prognostic biomarker in lung cancer patients.
Main Methods:
- Verified CYP2S1 expression using immunohistochemistry and Real-time PCR.
- Assessed cell proliferation, invasion, and migration in vitro via colony formation and Transwell assays.
- Evaluated tumor growth inhibition in vivo using xenograft models.
Main Results:
- CYP2S1 demonstrated significant upregulation in lung cancer tissues and cells.
- Downregulation of CYP2S1 inhibited lung cancer cell proliferation, invasion, and migration in vitro and tumor growth in vivo.
- Gene Set Enrichment Analysis (GSEA) implicated CYP2S1 in regulating E2F targets and the G2M checkpoint, crucial for cell cycle progression.
- Kaplan-Meier analysis revealed that elevated CYP2S1 expression correlated with significantly shorter overall survival (OS).
Conclusions:
- CYP2S1 functions as a tumor suppressor in lung cancer.
- High CYP2S1 expression serves as an unfavorable prognostic indicator for patient survival, suggesting its potential as a therapeutic target.
