ANO7 expression in the prostate modulates mitochondrial function and lipid metabolism
Abstract Background Prostate cancer (PrCa) is a significant health concern, ranking as the second most common cancer in males globally. Genetic factors contribute substantially to PrCa risk, with up to 57% of the risk being attributed to genetic determinants. A major challenge in managing PrCa is th...
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BMC
2025-02-01
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| Series: | Cell Communication and Signaling |
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| Online Access: | https://doi.org/10.1186/s12964-025-02081-7 |
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| author | Christoffer Löf Nasrin Sultana Neha Goel Samuel Heron Gudrun Wahlström Andrew House Minna Holopainen Reijo Käkelä Johanna Schleutker |
| author_facet | Christoffer Löf Nasrin Sultana Neha Goel Samuel Heron Gudrun Wahlström Andrew House Minna Holopainen Reijo Käkelä Johanna Schleutker |
| author_sort | Christoffer Löf |
| collection | DOAJ |
| description | Abstract Background Prostate cancer (PrCa) is a significant health concern, ranking as the second most common cancer in males globally. Genetic factors contribute substantially to PrCa risk, with up to 57% of the risk being attributed to genetic determinants. A major challenge in managing PrCa is the early identification of aggressive cases for targeted treatment, while avoiding unnecessary interventions in slow-progressing cases. Therefore, there is a critical need for genetic biomarkers that can distinguish between aggressive and non-aggressive PrCa cases. Previous research, including our own, has shown that germline variants in ANO7 are associated with aggressive PrCa. However, the function of ANO7 in the prostate remains unknown. Methods We performed RNA-sequencing (RNA-seq) on RWPE1 cells engineered to express ANO7 protein, alongside the analysis of a single-cell RNA-sequencing (scRNA-seq) dataset and RNA-seq from prostate tissues. Differential gene expression analysis and gene set enrichment analysis (GSEA) were conducted to identify key pathways. Additionally, we assessed oxidative phosphorylation (OXPHOS), glycolysis, and targeted metabolomics. Image analysis of mitochondrial morphology and lipidomics were also performed to provide further insight into the functional role of ANO7 in prostate cells. Results ANO7 expression resulted in the downregulation of metabolic pathways, particularly genes associated with the MYC pathway and oxidative phosphorylation (OXPHOS) in both prostate tissue and ANO7-expressing cells. Measurements of OXPHOS and glycolysis in the ANO7-expressing cells revealed a metabolic shift towards glycolysis. Targeted metabolomics showed reduced levels of the amino acid aspartate, indicating disrupted mitochondrial function in the ANO7-expressing cells. Image analysis demonstrated altered mitochondrial morphology in these cells. Additionally, ANO7 downregulated genes involved in fatty acid metabolism and induced changes in lipid composition of the cells, characterized by longer acyl chain lengths and increased unsaturation, suggesting a role for ANO7 in regulating lipid metabolism in the prostate. Conclusions This study provides new insights into the function of ANO7 in prostate cells, highlighting its involvement in metabolic pathways, particularly OXPHOS and lipid metabolism. The findings suggest that ANO7 may act as a key regulator of cellular lipid metabolism and mitochondrial function in the prostate, shedding light on a previously unknown aspect of ANO7’s biology. |
| format | Article |
| id | doaj-art-00f8061121004f7193d166183c82d0be |
| institution | Kabale University |
| issn | 1478-811X |
| language | English |
| publishDate | 2025-02-01 |
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| series | Cell Communication and Signaling |
| spelling | doaj-art-00f8061121004f7193d166183c82d0be2025-02-09T12:47:20ZengBMCCell Communication and Signaling1478-811X2025-02-0123111910.1186/s12964-025-02081-7ANO7 expression in the prostate modulates mitochondrial function and lipid metabolismChristoffer Löf0Nasrin Sultana1Neha Goel2Samuel Heron3Gudrun Wahlström4Andrew House5Minna Holopainen6Reijo Käkelä7Johanna Schleutker8Institute of Biomedicine, University of TurkuInstitute of Biomedicine, University of TurkuInstitute of Biomedicine, University of TurkuInstitute of Biomedicine, University of TurkuInstitute of Biomedicine, University of TurkuHelsinki University Lipidomics Unit (HiLIPID), Helsinki Institute of Life Science (HiLIFE) and Biocenter Finland, University of HelsinkiHelsinki University Lipidomics Unit (HiLIPID), Helsinki Institute of Life Science (HiLIFE) and Biocenter Finland, University of HelsinkiHelsinki University Lipidomics Unit (HiLIPID), Helsinki Institute of Life Science (HiLIFE) and Biocenter Finland, University of HelsinkiInstitute of Biomedicine, University of TurkuAbstract Background Prostate cancer (PrCa) is a significant health concern, ranking as the second most common cancer in males globally. Genetic factors contribute substantially to PrCa risk, with up to 57% of the risk being attributed to genetic determinants. A major challenge in managing PrCa is the early identification of aggressive cases for targeted treatment, while avoiding unnecessary interventions in slow-progressing cases. Therefore, there is a critical need for genetic biomarkers that can distinguish between aggressive and non-aggressive PrCa cases. Previous research, including our own, has shown that germline variants in ANO7 are associated with aggressive PrCa. However, the function of ANO7 in the prostate remains unknown. Methods We performed RNA-sequencing (RNA-seq) on RWPE1 cells engineered to express ANO7 protein, alongside the analysis of a single-cell RNA-sequencing (scRNA-seq) dataset and RNA-seq from prostate tissues. Differential gene expression analysis and gene set enrichment analysis (GSEA) were conducted to identify key pathways. Additionally, we assessed oxidative phosphorylation (OXPHOS), glycolysis, and targeted metabolomics. Image analysis of mitochondrial morphology and lipidomics were also performed to provide further insight into the functional role of ANO7 in prostate cells. Results ANO7 expression resulted in the downregulation of metabolic pathways, particularly genes associated with the MYC pathway and oxidative phosphorylation (OXPHOS) in both prostate tissue and ANO7-expressing cells. Measurements of OXPHOS and glycolysis in the ANO7-expressing cells revealed a metabolic shift towards glycolysis. Targeted metabolomics showed reduced levels of the amino acid aspartate, indicating disrupted mitochondrial function in the ANO7-expressing cells. Image analysis demonstrated altered mitochondrial morphology in these cells. Additionally, ANO7 downregulated genes involved in fatty acid metabolism and induced changes in lipid composition of the cells, characterized by longer acyl chain lengths and increased unsaturation, suggesting a role for ANO7 in regulating lipid metabolism in the prostate. Conclusions This study provides new insights into the function of ANO7 in prostate cells, highlighting its involvement in metabolic pathways, particularly OXPHOS and lipid metabolism. The findings suggest that ANO7 may act as a key regulator of cellular lipid metabolism and mitochondrial function in the prostate, shedding light on a previously unknown aspect of ANO7’s biology.https://doi.org/10.1186/s12964-025-02081-7Prostate cancerANO7MitochondriaLipid metabolismMYCOXPHOS |
| spellingShingle | Christoffer Löf Nasrin Sultana Neha Goel Samuel Heron Gudrun Wahlström Andrew House Minna Holopainen Reijo Käkelä Johanna Schleutker ANO7 expression in the prostate modulates mitochondrial function and lipid metabolism Cell Communication and Signaling Prostate cancer ANO7 Mitochondria Lipid metabolism MYC OXPHOS |
| title | ANO7 expression in the prostate modulates mitochondrial function and lipid metabolism |
| title_full | ANO7 expression in the prostate modulates mitochondrial function and lipid metabolism |
| title_fullStr | ANO7 expression in the prostate modulates mitochondrial function and lipid metabolism |
| title_full_unstemmed | ANO7 expression in the prostate modulates mitochondrial function and lipid metabolism |
| title_short | ANO7 expression in the prostate modulates mitochondrial function and lipid metabolism |
| title_sort | ano7 expression in the prostate modulates mitochondrial function and lipid metabolism |
| topic | Prostate cancer ANO7 Mitochondria Lipid metabolism MYC OXPHOS |
| url | https://doi.org/10.1186/s12964-025-02081-7 |
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