Cuproptosis-related lncRNAs emerge as a novel signature for predicting prognosis in prostate carcinoma and functional experimental validation
BackgroundProstate cancer (PCa) is one of the most common malignancies of the urinary system. Cuproptosis, a newly discovered form of cell death. The relationship between cuproptosis-related long non-coding RNAs (ClncRNAs) related to PCa and prognosis remains unclear. This study aimed to explore the...
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Frontiers Media S.A.
2024-10-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1471198/full |
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| author | Yangbai- Lu Jinfeng- Wu Xianzhe Li Xianzhe Li Qu- Leng Jian- Tan Hongxing- Huang Rui- Zhong Zhenjie- Chen Yongxin- Zhang |
| author_facet | Yangbai- Lu Jinfeng- Wu Xianzhe Li Xianzhe Li Qu- Leng Jian- Tan Hongxing- Huang Rui- Zhong Zhenjie- Chen Yongxin- Zhang |
| author_sort | Yangbai- Lu |
| collection | DOAJ |
| description | BackgroundProstate cancer (PCa) is one of the most common malignancies of the urinary system. Cuproptosis, a newly discovered form of cell death. The relationship between cuproptosis-related long non-coding RNAs (ClncRNAs) related to PCa and prognosis remains unclear. This study aimed to explore the clinical significance of novel ClncRNAs in the prognostic assessment of PCa.MethodsClncRNAs and differentially expressed mRNAs linked to these ClncRNAs were identified using Pearson’s correlation and differential expression analyses. A prognostic signature (risk score) comprising three ClncRNAs was established based on multivariable Cox regression analysis. The predictive performance of this ClncRNAs signature was validated using receiver operating characteristic curves and nomograms. Finally, further in vitro cell experiments were conducted for validation, including quantitative polymerase chain reaction (qPCR), western blot (WB), cell proliferation assays, cell migration assays, cell invasion assays, apoptosis, and cell cycle analysis.ResultsWe constructed a prognostic signature of ClncRNAs for PCa comprising three key differentially expressed ClncRNAs(AC010896-1, AC016394-2, and SNHG9). Multivariable Cox regression analysis indicated that clinical staging and risk scores of the ClncRNAs signature were independent prognostic factors for PCa. Compared to other clinical features, the ClncRNAs signature exhibited higher diagnostic efficiency and performed well in predicting the 1-, 3-, and 5-year progression-free intervals (PFIs) for PCa. Notably, in terms of immune activity, PCa patients with high-risk scores exhibited higher tumor mutational burden (TMB) levels, while their Tumor Immune Dysfunction and Exclusion (TIDE) scores were lower than those of PCa patients with low-risk scores. Additionally, in vitro cellular functional experiments, we knocked down SNHG9 that is the most significantly differentially expressed ClncRNA among the three key ClncRNAs. SNHG9 knockdown resulted in a significant increase in G1 phase cells and a decrease in S and G2 phases, indicating inhibition of DNA synthesis and cell cycle progression. Colony formation assays showed reduced clonogenic ability, with fewer and smaller colonies. Western blot analysis revealed the upregulation of the key cuproptosis-related mRNAs FDX1 and DLST. These findings suggested that SNHG9 promotes PCa cell proliferation, migration, and invasion.ConclusionBuilding on the three ClncRNAs, we identified a novel prognostic signature of PCa. The ClncRNA SNHG9 can promote PCa cell proliferation, migration, and invasion. |
| format | Article |
| id | doaj-art-c18799eec3f84cc486dee94354735f08 |
| institution | OA Journals |
| issn | 1664-3224 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-c18799eec3f84cc486dee94354735f082025-08-20T02:11:16ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-10-011510.3389/fimmu.2024.14711981471198Cuproptosis-related lncRNAs emerge as a novel signature for predicting prognosis in prostate carcinoma and functional experimental validationYangbai- Lu0Jinfeng- Wu1Xianzhe Li2Xianzhe Li3Qu- Leng4Jian- Tan5Hongxing- Huang6Rui- Zhong7Zhenjie- Chen8Yongxin- Zhang9Department of Urology, Zhongshan City People’s Hospital, Zhongshan, Guangdong, ChinaDepartment of First Clinical Medical College, Guangdong Medical University, Zhanjiang, Guangdong, ChinaDivision of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, GermanyMedical Faculty Heidelberg, Heidelberg University, Heidelberg, GermanyDepartment of Urology, Zhongshan City People’s Hospital, Zhongshan, Guangdong, ChinaDepartment of First Clinical Medical College, Guangdong Medical University, Zhanjiang, Guangdong, ChinaDepartment of Urology, Zhongshan City People’s Hospital, Zhongshan, Guangdong, ChinaDepartment of Urology, Zhongshan City People’s Hospital, Zhongshan, Guangdong, ChinaDepartment of Urology, Zhongshan City People’s Hospital, Zhongshan, Guangdong, ChinaDepartment of MR, Zhongshan City People’s Hospital, Zhongshan, Guangdong, ChinaBackgroundProstate cancer (PCa) is one of the most common malignancies of the urinary system. Cuproptosis, a newly discovered form of cell death. The relationship between cuproptosis-related long non-coding RNAs (ClncRNAs) related to PCa and prognosis remains unclear. This study aimed to explore the clinical significance of novel ClncRNAs in the prognostic assessment of PCa.MethodsClncRNAs and differentially expressed mRNAs linked to these ClncRNAs were identified using Pearson’s correlation and differential expression analyses. A prognostic signature (risk score) comprising three ClncRNAs was established based on multivariable Cox regression analysis. The predictive performance of this ClncRNAs signature was validated using receiver operating characteristic curves and nomograms. Finally, further in vitro cell experiments were conducted for validation, including quantitative polymerase chain reaction (qPCR), western blot (WB), cell proliferation assays, cell migration assays, cell invasion assays, apoptosis, and cell cycle analysis.ResultsWe constructed a prognostic signature of ClncRNAs for PCa comprising three key differentially expressed ClncRNAs(AC010896-1, AC016394-2, and SNHG9). Multivariable Cox regression analysis indicated that clinical staging and risk scores of the ClncRNAs signature were independent prognostic factors for PCa. Compared to other clinical features, the ClncRNAs signature exhibited higher diagnostic efficiency and performed well in predicting the 1-, 3-, and 5-year progression-free intervals (PFIs) for PCa. Notably, in terms of immune activity, PCa patients with high-risk scores exhibited higher tumor mutational burden (TMB) levels, while their Tumor Immune Dysfunction and Exclusion (TIDE) scores were lower than those of PCa patients with low-risk scores. Additionally, in vitro cellular functional experiments, we knocked down SNHG9 that is the most significantly differentially expressed ClncRNA among the three key ClncRNAs. SNHG9 knockdown resulted in a significant increase in G1 phase cells and a decrease in S and G2 phases, indicating inhibition of DNA synthesis and cell cycle progression. Colony formation assays showed reduced clonogenic ability, with fewer and smaller colonies. Western blot analysis revealed the upregulation of the key cuproptosis-related mRNAs FDX1 and DLST. These findings suggested that SNHG9 promotes PCa cell proliferation, migration, and invasion.ConclusionBuilding on the three ClncRNAs, we identified a novel prognostic signature of PCa. The ClncRNA SNHG9 can promote PCa cell proliferation, migration, and invasion.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1471198/fullcuproptosislncRNAsprognosis signatureprostate carcinomaSNHG9 |
| spellingShingle | Yangbai- Lu Jinfeng- Wu Xianzhe Li Xianzhe Li Qu- Leng Jian- Tan Hongxing- Huang Rui- Zhong Zhenjie- Chen Yongxin- Zhang Cuproptosis-related lncRNAs emerge as a novel signature for predicting prognosis in prostate carcinoma and functional experimental validation Frontiers in Immunology cuproptosis lncRNAs prognosis signature prostate carcinoma SNHG9 |
| title | Cuproptosis-related lncRNAs emerge as a novel signature for predicting prognosis in prostate carcinoma and functional experimental validation |
| title_full | Cuproptosis-related lncRNAs emerge as a novel signature for predicting prognosis in prostate carcinoma and functional experimental validation |
| title_fullStr | Cuproptosis-related lncRNAs emerge as a novel signature for predicting prognosis in prostate carcinoma and functional experimental validation |
| title_full_unstemmed | Cuproptosis-related lncRNAs emerge as a novel signature for predicting prognosis in prostate carcinoma and functional experimental validation |
| title_short | Cuproptosis-related lncRNAs emerge as a novel signature for predicting prognosis in prostate carcinoma and functional experimental validation |
| title_sort | cuproptosis related lncrnas emerge as a novel signature for predicting prognosis in prostate carcinoma and functional experimental validation |
| topic | cuproptosis lncRNAs prognosis signature prostate carcinoma SNHG9 |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1471198/full |
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