Endoplasmic reticulum stress-related CLIP4 plays a procarcinogenic role in hepatocellular carcinoma: an integrated analysis
Abstract Objective To explore the potential of endoplasmic reticulum stress (ERS)-associated protein CLIP4 as a biomarker for hepatocellular carcinoma (HCC) and the underlying mechanism. Methods TCGA public database and a tissue microarray were used to investigate the molecular characteristics of CL...
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BMC
2025-02-01
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| Series: | BMC Cancer |
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| Online Access: | https://doi.org/10.1186/s12885-025-13537-x |
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| author | Anqi Wang Sitong Yan Weijia Jiang Xiang Chen Yuhan Huang Xiangyu Zu Xiao Du Lulu Fan Jiatao Liu Guoping Sun |
| author_facet | Anqi Wang Sitong Yan Weijia Jiang Xiang Chen Yuhan Huang Xiangyu Zu Xiao Du Lulu Fan Jiatao Liu Guoping Sun |
| author_sort | Anqi Wang |
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| description | Abstract Objective To explore the potential of endoplasmic reticulum stress (ERS)-associated protein CLIP4 as a biomarker for hepatocellular carcinoma (HCC) and the underlying mechanism. Methods TCGA public database and a tissue microarray were used to investigate the molecular characteristics of CLIP4 and its association with disease. TCGA-LIHC dataset was used for single-gene differential expression analysis, single-gene correlation analysis, functional enrichment analysis, immune infiltration analysis, and DNA methylation analysis. RNA-seq, immunohistochemistry, western blotting, and RT-qPCR were used to verify the effect of ERS on CLIP4 expression. Public databases and miRNA-seq data were used to explore the TF-miRNA-CLIP4 regulatory network. CCK-8, colony formation, EdU staining, wound-healing, Transwell, western blotting and RT-qPCR were used to detect the effects of CLIP4 on the proliferation, migration and epithelial-mesenchymal transition (EMT) of HCC cells. Results Analysis of TCGA datasets and tissue microarrays demonstrated that elevated CLIP4 expression was associated with poor prognosis in HCC. Enrichment analysis revealed that CLIP4 is involved in the immune response, cell adhesion, and EMT. There was a positive correlation between CLIP4 expression and the infiltration of the majority of immune cells, immunomodulators, and chemokines. Furthermore, the DNA methylation pattern of CLIP4 was found to have significant prognostic value. ERS was found to significantly upregulate CLIP4 expression. In addition, the ERS-RELA-miR-222-5p-CLIP4 transcriptional network was constructed to clarify the role of CLIP4. Cell function experiments confirmed that it promotes the proliferation, migration, and EMT of HCC cells. Conclusions CLIP4 is a potential immune-related oncogenic molecule in HCC. ERS regulates the expression of CLIP4, and CLIP4 promotes the proliferation, migration, and EMT of HCC cells. |
| format | Article |
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| institution | Kabale University |
| issn | 1471-2407 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
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| series | BMC Cancer |
| spelling | doaj-art-b6882e4d8afe4edaa1542630931bdb742025-02-09T12:41:45ZengBMCBMC Cancer1471-24072025-02-0125112010.1186/s12885-025-13537-xEndoplasmic reticulum stress-related CLIP4 plays a procarcinogenic role in hepatocellular carcinoma: an integrated analysisAnqi Wang0Sitong Yan1Weijia Jiang2Xiang Chen3Yuhan Huang4Xiangyu Zu5Xiao Du6Lulu Fan7Jiatao Liu8Guoping Sun9Department of Oncology, The First Affiliated Hospital of Anhui Medical UniversityDepartment of Oncology, The First Affiliated Hospital of Anhui Medical UniversityDepartment of Oncology, The First Affiliated Hospital of Anhui Medical UniversityDepartment of Oncology, The First Affiliated Hospital of Anhui Medical UniversityDepartment of Oncology, The First Affiliated Hospital of Anhui Medical UniversityDepartment of Oncology, The First Affiliated Hospital of Anhui Medical UniversityDepartment of Oncology, The First Affiliated Hospital of Anhui Medical UniversityDepartment of Oncology, The First Affiliated Hospital of Anhui Medical UniversityDepartment of Pharmacy, The First Affiliated Hospital of Anhui Medical UniversityDepartment of Oncology, The First Affiliated Hospital of Anhui Medical UniversityAbstract Objective To explore the potential of endoplasmic reticulum stress (ERS)-associated protein CLIP4 as a biomarker for hepatocellular carcinoma (HCC) and the underlying mechanism. Methods TCGA public database and a tissue microarray were used to investigate the molecular characteristics of CLIP4 and its association with disease. TCGA-LIHC dataset was used for single-gene differential expression analysis, single-gene correlation analysis, functional enrichment analysis, immune infiltration analysis, and DNA methylation analysis. RNA-seq, immunohistochemistry, western blotting, and RT-qPCR were used to verify the effect of ERS on CLIP4 expression. Public databases and miRNA-seq data were used to explore the TF-miRNA-CLIP4 regulatory network. CCK-8, colony formation, EdU staining, wound-healing, Transwell, western blotting and RT-qPCR were used to detect the effects of CLIP4 on the proliferation, migration and epithelial-mesenchymal transition (EMT) of HCC cells. Results Analysis of TCGA datasets and tissue microarrays demonstrated that elevated CLIP4 expression was associated with poor prognosis in HCC. Enrichment analysis revealed that CLIP4 is involved in the immune response, cell adhesion, and EMT. There was a positive correlation between CLIP4 expression and the infiltration of the majority of immune cells, immunomodulators, and chemokines. Furthermore, the DNA methylation pattern of CLIP4 was found to have significant prognostic value. ERS was found to significantly upregulate CLIP4 expression. In addition, the ERS-RELA-miR-222-5p-CLIP4 transcriptional network was constructed to clarify the role of CLIP4. Cell function experiments confirmed that it promotes the proliferation, migration, and EMT of HCC cells. Conclusions CLIP4 is a potential immune-related oncogenic molecule in HCC. ERS regulates the expression of CLIP4, and CLIP4 promotes the proliferation, migration, and EMT of HCC cells.https://doi.org/10.1186/s12885-025-13537-xHepatocellular carcinomaEndoplasmic reticulum stressCLIP4Bioinformatics analysisEpithelial-mesenchymal transition |
| spellingShingle | Anqi Wang Sitong Yan Weijia Jiang Xiang Chen Yuhan Huang Xiangyu Zu Xiao Du Lulu Fan Jiatao Liu Guoping Sun Endoplasmic reticulum stress-related CLIP4 plays a procarcinogenic role in hepatocellular carcinoma: an integrated analysis BMC Cancer Hepatocellular carcinoma Endoplasmic reticulum stress CLIP4 Bioinformatics analysis Epithelial-mesenchymal transition |
| title | Endoplasmic reticulum stress-related CLIP4 plays a procarcinogenic role in hepatocellular carcinoma: an integrated analysis |
| title_full | Endoplasmic reticulum stress-related CLIP4 plays a procarcinogenic role in hepatocellular carcinoma: an integrated analysis |
| title_fullStr | Endoplasmic reticulum stress-related CLIP4 plays a procarcinogenic role in hepatocellular carcinoma: an integrated analysis |
| title_full_unstemmed | Endoplasmic reticulum stress-related CLIP4 plays a procarcinogenic role in hepatocellular carcinoma: an integrated analysis |
| title_short | Endoplasmic reticulum stress-related CLIP4 plays a procarcinogenic role in hepatocellular carcinoma: an integrated analysis |
| title_sort | endoplasmic reticulum stress related clip4 plays a procarcinogenic role in hepatocellular carcinoma an integrated analysis |
| topic | Hepatocellular carcinoma Endoplasmic reticulum stress CLIP4 Bioinformatics analysis Epithelial-mesenchymal transition |
| url | https://doi.org/10.1186/s12885-025-13537-x |
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