Downregulation of PGK1 promotes lipid peroxidation and suppresses proliferation in cervical cancer revealed by liquid-liquid phase separation-related gene signature
Abstract Cervix cancer is a major health concern globally, being the fourth most prevalent type of cancer among females across the globe. Despite existing preventive measures like cytology and HPV testing, more precise diagnostic and treatment strategies are needed. This study leverages single-cell...
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| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-08-01
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| Series: | BMC Cancer |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12885-025-14637-4 |
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| Summary: | Abstract Cervix cancer is a major health concern globally, being the fourth most prevalent type of cancer among females across the globe. Despite existing preventive measures like cytology and HPV testing, more precise diagnostic and treatment strategies are needed. This study leverages single-cell sequencing and transcriptome analysis to identify LLPS-linked therapeutic targets in cervical cancer. Utilizing data from the GEO database, we characterized six main cell types in cervical cancer and calculated LLPS scores for each. Analysis of LLPS-related genes revealed seven prognostic genes, and we constructed a predictive model demonstrating promising stability and accuracy. Furthermore, high-risk patients exhibited higher LLPS scores and lower survival probabilities, which may be influenced by differences in the tumor immune microenvironment, particularly involving immune cell types such as CD8+ T cells, M0 macrophages and regulatory T cells. Exploring the expression patterns of model genes, we found PDIA6, PGK1, ASPH, and FNDC3B to be involved in immune infiltration during tumorigenesis. Finally, the signature genes that related to immune microenvironment was confirmed by immunohistochemistry staining. PGK1 was found to be most closely associated with the prognosis of cervical cancer. The correlation analysis of PGK1 with pathways in cervical cancer revealed that the expression level of PGK1 is associated with lipid peroxidation. Furthermore, our analysis using immunofluorescence and flow cytometry showed that lipid peroxidation increased after PGK1 knockdown. We further employed the proliferation experiment and cell-derived xenograft (CDX) mouse model to verify that downregulating PGK1 suppresses proliferation of cervical cancer in vitro and in vivo. Taken together, our study provides comprehensive insights into cervical cancer prognosis, identifying PGK1 as a potential therapeutic target among LLPS-related genes. |
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| ISSN: | 1471-2407 |