circASAP1 induces renal clear cell carcinoma ferroptosis by binding to HNRNPC and thereby regulating GPX4
Abstract Background Clear cell renal cell carcinoma (ccRCC) represents the most prevalent subtype, accounting for nearly 80% of all RCC cases. Recent research has shown that high expression of circular non-coding RNA (circRNA) is associated with poor prognosis in patients with renal clear cell carci...
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BMC
2025-01-01
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| Series: | Molecular Cancer |
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| Online Access: | https://doi.org/10.1186/s12943-024-02122-8 |
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| author | Yunfei Wang Taowei Yang Qihao Li Zhousan Zheng Lican Liao Junjie Cen Wei Chen Junhang Luo Yi Xu Mi Zhou Jiaxing Zhang |
| author_facet | Yunfei Wang Taowei Yang Qihao Li Zhousan Zheng Lican Liao Junjie Cen Wei Chen Junhang Luo Yi Xu Mi Zhou Jiaxing Zhang |
| author_sort | Yunfei Wang |
| collection | DOAJ |
| description | Abstract Background Clear cell renal cell carcinoma (ccRCC) represents the most prevalent subtype, accounting for nearly 80% of all RCC cases. Recent research has shown that high expression of circular non-coding RNA (circRNA) is associated with poor prognosis in patients with renal clear cell carcinoma (ccRCC), however, the underlying mechanism remains unclear. Methods After analysing self-sequenced renal cancer and paracancer circRNA sequencing data and comparing it with the GEO public database, we discovered that circASAP1 expression was significantly up-regulated in renal cancers. We also tested circASAP1 levels in 102 renal cancer patients and found that high expression of circASAP1 was associated with poor prognosis and metastasis. The interaction between circASAP1, HNRNPC and their downstream target genes was confirmed through experiments such as RNA pull-down, RIP and fluorescence in situ hybridisation. A series of in vitro and in vivo functional experiments were performed to verify the effects of circASAP1 on RCC proliferation and metastasis. Results Circular RNA sequencing analysis revealed that circASAP1 expression was markedly elevated in ccRCC, with a significant association observed between elevated circASAP1 expression and poor prognosis and metastasis. Actinomycin D, RNase R, as well as fluorescence in situ hybridization (FISH) analyses revealed the ring structure and cytoplasmic localization of circASAP1. High circASAP1 expression was associated with ccRCC cell proliferative viability, invasion, and metastasis in CCK-8, transwell, plate cloning, and EdU experiments. Interaction of circASAP1 with HNRNPC and their downstream target genes was confirmed by RNA pull-down, RNA immunoprecipitation, FISH, silver staining, and mass spectrometry. Experiments using truncated isoforms demonstrated that amino acids 16–87 of HNRNPC bound circASAP1. Proteins altered by circASAP1 were enriched in the ferroptosis pathway on the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. Conclusions The relationship between circRNA and the ASAP1/HNRNPC/GPX4 axis was demonstrated by experimental data, which was further confirmed by rescue experiments. circASAP1 influenced tumor growth and ferroptosis in animal experiments and predicted the prognosis of patients with ccRCC. The circASAP1/HNRNPC/GPX4 axis provides novel directions and potential targets for RCC treatment. |
| format | Article |
| id | doaj-art-9e42a5c111374452a6d33fab6fec92c2 |
| institution | Kabale University |
| issn | 1476-4598 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Cancer |
| spelling | doaj-art-9e42a5c111374452a6d33fab6fec92c22025-01-05T12:10:23ZengBMCMolecular Cancer1476-45982025-01-0124112010.1186/s12943-024-02122-8circASAP1 induces renal clear cell carcinoma ferroptosis by binding to HNRNPC and thereby regulating GPX4Yunfei Wang0Taowei Yang1Qihao Li2Zhousan Zheng3Lican Liao4Junjie Cen5Wei Chen6Junhang Luo7Yi Xu8Mi Zhou9Jiaxing Zhang10Department of Oncology, The First Affiliated Hospital of Sun Yat-sen UniversityDepartment of Urology, The First Affiliated Hospital of Sun Yat-sen UniversityDepartment of Urology, The First Affiliated Hospital of Sun Yat-sen UniversityDepartment of Oncology, The First Affiliated Hospital of Sun Yat-sen UniversityDepartment of Oncology, The First Affiliated Hospital of Sun Yat-sen UniversityDepartment of Urology, The First Affiliated Hospital of Sun Yat-sen UniversityDepartment of Urology, The First Affiliated Hospital of Sun Yat-sen UniversityDepartment of Urology, The First Affiliated Hospital of Sun Yat-sen UniversityDepartment of Breast and Thyroid Surgery, Guangzhou Women and Children’s Medical CenterDepartment of Oncology, The First Affiliated Hospital of Sun Yat-sen UniversityDepartment of Oncology, The First Affiliated Hospital of Sun Yat-sen UniversityAbstract Background Clear cell renal cell carcinoma (ccRCC) represents the most prevalent subtype, accounting for nearly 80% of all RCC cases. Recent research has shown that high expression of circular non-coding RNA (circRNA) is associated with poor prognosis in patients with renal clear cell carcinoma (ccRCC), however, the underlying mechanism remains unclear. Methods After analysing self-sequenced renal cancer and paracancer circRNA sequencing data and comparing it with the GEO public database, we discovered that circASAP1 expression was significantly up-regulated in renal cancers. We also tested circASAP1 levels in 102 renal cancer patients and found that high expression of circASAP1 was associated with poor prognosis and metastasis. The interaction between circASAP1, HNRNPC and their downstream target genes was confirmed through experiments such as RNA pull-down, RIP and fluorescence in situ hybridisation. A series of in vitro and in vivo functional experiments were performed to verify the effects of circASAP1 on RCC proliferation and metastasis. Results Circular RNA sequencing analysis revealed that circASAP1 expression was markedly elevated in ccRCC, with a significant association observed between elevated circASAP1 expression and poor prognosis and metastasis. Actinomycin D, RNase R, as well as fluorescence in situ hybridization (FISH) analyses revealed the ring structure and cytoplasmic localization of circASAP1. High circASAP1 expression was associated with ccRCC cell proliferative viability, invasion, and metastasis in CCK-8, transwell, plate cloning, and EdU experiments. Interaction of circASAP1 with HNRNPC and their downstream target genes was confirmed by RNA pull-down, RNA immunoprecipitation, FISH, silver staining, and mass spectrometry. Experiments using truncated isoforms demonstrated that amino acids 16–87 of HNRNPC bound circASAP1. Proteins altered by circASAP1 were enriched in the ferroptosis pathway on the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. Conclusions The relationship between circRNA and the ASAP1/HNRNPC/GPX4 axis was demonstrated by experimental data, which was further confirmed by rescue experiments. circASAP1 influenced tumor growth and ferroptosis in animal experiments and predicted the prognosis of patients with ccRCC. The circASAP1/HNRNPC/GPX4 axis provides novel directions and potential targets for RCC treatment.https://doi.org/10.1186/s12943-024-02122-8Renal cell carcinomaCircASAP1HNRNPCFerroptosis |
| spellingShingle | Yunfei Wang Taowei Yang Qihao Li Zhousan Zheng Lican Liao Junjie Cen Wei Chen Junhang Luo Yi Xu Mi Zhou Jiaxing Zhang circASAP1 induces renal clear cell carcinoma ferroptosis by binding to HNRNPC and thereby regulating GPX4 Molecular Cancer Renal cell carcinoma CircASAP1 HNRNPC Ferroptosis |
| title | circASAP1 induces renal clear cell carcinoma ferroptosis by binding to HNRNPC and thereby regulating GPX4 |
| title_full | circASAP1 induces renal clear cell carcinoma ferroptosis by binding to HNRNPC and thereby regulating GPX4 |
| title_fullStr | circASAP1 induces renal clear cell carcinoma ferroptosis by binding to HNRNPC and thereby regulating GPX4 |
| title_full_unstemmed | circASAP1 induces renal clear cell carcinoma ferroptosis by binding to HNRNPC and thereby regulating GPX4 |
| title_short | circASAP1 induces renal clear cell carcinoma ferroptosis by binding to HNRNPC and thereby regulating GPX4 |
| title_sort | circasap1 induces renal clear cell carcinoma ferroptosis by binding to hnrnpc and thereby regulating gpx4 |
| topic | Renal cell carcinoma CircASAP1 HNRNPC Ferroptosis |
| url | https://doi.org/10.1186/s12943-024-02122-8 |
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