Noxa inhibits oncogenesis through ZNF519 in gastric cancer and is suppressed by hsa-miR-200b-3p
Abstract While Phorbol-12-myristate-13-acetate-induced protein 1 (Noxa/PMAIP1) assumes a pivotal role in numerous tumors, its clinical implications and underlying mechanisms of gastric cancer (GC) are yet enigmatic. In this investigation, our primary objective was to scrutinize the clinical relevanc...
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| Format: | Article |
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Nature Portfolio
2024-03-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-024-57099-7 |
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| author | Jin Shi Fan Ding Dezhu Dai Xudong Song Xu Wu Dongsheng Yan Xiao Han Guoquan Tao Weijie Dai |
| author_facet | Jin Shi Fan Ding Dezhu Dai Xudong Song Xu Wu Dongsheng Yan Xiao Han Guoquan Tao Weijie Dai |
| author_sort | Jin Shi |
| collection | DOAJ |
| description | Abstract While Phorbol-12-myristate-13-acetate-induced protein 1 (Noxa/PMAIP1) assumes a pivotal role in numerous tumors, its clinical implications and underlying mechanisms of gastric cancer (GC) are yet enigmatic. In this investigation, our primary objective was to scrutinize the clinical relevance and potential mechanisms of Noxa in gastric cancer. Immunohistochemical analysis was conducted on tissue microarrays comprising samples from a meticulously characterized cohort of 84 gastric cancer patients, accompanied by follow-up data, to assess the expression of Noxa. Additionally, Noxa expression levels in gastric cancer clinical samples and cell lines were measured through quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis. The effect of Noxa expression on the prognosis of patients with gastric cancer was evaluated using Kaplan–Meier survival. Further insight into the role of Noxa in driving gastric cancer progression was gained through an array of experimental techniques, including cell viability assays (CCK8), plate cloning assays, transwell assays, scratch assays, and real-time cell analysis (RTCA). Potential upstream microRNAs (miRNAs) that might modulate Noxa were identified through rigorous bioinformatics analysis, substantiated by luciferase reporter assays and Western blot experiments. Additionally, we utilized RNA sequencing, qRT-PCR, and Western blot to identify proteins binding to Noxa and potential downstream target. Finally, we utilized BALB/c nude mice to explore the role of Noxa in vivo. Our investigation unveiled a marked downregulation of Noxa expression in gastric cancer and underscored its significance as a pivotal prognostic factor influencing overall survival (OS). Noxa overexpression exerted a substantial inhibitory effect on the proliferation, migration and invasion of GC cells. Bioinformatic analysis and dual luciferase reporter assays unveiled the capacity of hsa-miR-200b-3p to interact with the 3′-UTR of Noxa mRNA, thereby orchestrating a downregulation of Noxa expression in vitro, consequently promoting tumor progression in GC. Our transcriptome analysis, coupled with mechanistic validation, elucidated a role for Noxa in modulating the expression of ZNF519 in the Mitophagy-animal pathway. The depletion of ZNF519 effectively reversed the oncogenic attributes induced by Noxa. Upregulation of Noxa expression suppressed the tumorigenesis of GC in vivo. The current investigation sheds light on the pivotal role of the hsa-miR-200b-3p/Noxa/ZNF519 axis in elucidating the pathogenesis of gastric cancer, offering a promising avenue for targeted therapeutic interventions in the management of this challenging malignancy. |
| first_indexed | 2024-04-24T19:55:54Z |
| format | Article |
| id | doaj.art-4ba4a1bb770640ae8e00057c35e2d217 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-24T19:55:54Z |
| publishDate | 2024-03-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj.art-4ba4a1bb770640ae8e00057c35e2d2172024-03-24T12:19:38ZengNature PortfolioScientific Reports2045-23222024-03-0114111610.1038/s41598-024-57099-7Noxa inhibits oncogenesis through ZNF519 in gastric cancer and is suppressed by hsa-miR-200b-3pJin Shi0Fan Ding1Dezhu Dai2Xudong Song3Xu Wu4Dongsheng Yan5Xiao Han6Guoquan Tao7Weijie Dai8Department of Gastrointestinal Surgery, The Affiliated Huaian No. 1 People’s Hospital of Nanjing Medical UniversityDepartment of Gastrointestinal Surgery, The Affiliated Huaian No. 1 People’s Hospital of Nanjing Medical UniversityDepartment of Gastrointestinal Surgery, The Affiliated Huaian No. 1 People’s Hospital of Nanjing Medical UniversityDepartment of Gastrointestinal Surgery, The Affiliated Huaian No. 1 People’s Hospital of Nanjing Medical UniversityDepartment of Vascular, Huaian Hospital Affiliated to Xuzhou Medical UniversityDepartment of Gastrointestinal Surgery, The Affiliated Huaian No. 1 People’s Hospital of Nanjing Medical UniversityDepartment of Gastrointestinal Surgery, The Affiliated Huaian No. 1 People’s Hospital of Nanjing Medical UniversityDepartment of Gastrointestinal Surgery, The Affiliated Huaian No. 1 People’s Hospital of Nanjing Medical UniversityDepartment of Gastroenterology, The Affiliated Huaian No. 1 People’s Hospital of Nanjing Medical UniversityAbstract While Phorbol-12-myristate-13-acetate-induced protein 1 (Noxa/PMAIP1) assumes a pivotal role in numerous tumors, its clinical implications and underlying mechanisms of gastric cancer (GC) are yet enigmatic. In this investigation, our primary objective was to scrutinize the clinical relevance and potential mechanisms of Noxa in gastric cancer. Immunohistochemical analysis was conducted on tissue microarrays comprising samples from a meticulously characterized cohort of 84 gastric cancer patients, accompanied by follow-up data, to assess the expression of Noxa. Additionally, Noxa expression levels in gastric cancer clinical samples and cell lines were measured through quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis. The effect of Noxa expression on the prognosis of patients with gastric cancer was evaluated using Kaplan–Meier survival. Further insight into the role of Noxa in driving gastric cancer progression was gained through an array of experimental techniques, including cell viability assays (CCK8), plate cloning assays, transwell assays, scratch assays, and real-time cell analysis (RTCA). Potential upstream microRNAs (miRNAs) that might modulate Noxa were identified through rigorous bioinformatics analysis, substantiated by luciferase reporter assays and Western blot experiments. Additionally, we utilized RNA sequencing, qRT-PCR, and Western blot to identify proteins binding to Noxa and potential downstream target. Finally, we utilized BALB/c nude mice to explore the role of Noxa in vivo. Our investigation unveiled a marked downregulation of Noxa expression in gastric cancer and underscored its significance as a pivotal prognostic factor influencing overall survival (OS). Noxa overexpression exerted a substantial inhibitory effect on the proliferation, migration and invasion of GC cells. Bioinformatic analysis and dual luciferase reporter assays unveiled the capacity of hsa-miR-200b-3p to interact with the 3′-UTR of Noxa mRNA, thereby orchestrating a downregulation of Noxa expression in vitro, consequently promoting tumor progression in GC. Our transcriptome analysis, coupled with mechanistic validation, elucidated a role for Noxa in modulating the expression of ZNF519 in the Mitophagy-animal pathway. The depletion of ZNF519 effectively reversed the oncogenic attributes induced by Noxa. Upregulation of Noxa expression suppressed the tumorigenesis of GC in vivo. The current investigation sheds light on the pivotal role of the hsa-miR-200b-3p/Noxa/ZNF519 axis in elucidating the pathogenesis of gastric cancer, offering a promising avenue for targeted therapeutic interventions in the management of this challenging malignancy.https://doi.org/10.1038/s41598-024-57099-7Gastric cancerNoxaHsa-miR-200b-3pZNF519PrognosisProliferation |
| spellingShingle | Jin Shi Fan Ding Dezhu Dai Xudong Song Xu Wu Dongsheng Yan Xiao Han Guoquan Tao Weijie Dai Noxa inhibits oncogenesis through ZNF519 in gastric cancer and is suppressed by hsa-miR-200b-3p Scientific Reports Gastric cancer Noxa Hsa-miR-200b-3p ZNF519 Prognosis Proliferation |
| title | Noxa inhibits oncogenesis through ZNF519 in gastric cancer and is suppressed by hsa-miR-200b-3p |
| title_full | Noxa inhibits oncogenesis through ZNF519 in gastric cancer and is suppressed by hsa-miR-200b-3p |
| title_fullStr | Noxa inhibits oncogenesis through ZNF519 in gastric cancer and is suppressed by hsa-miR-200b-3p |
| title_full_unstemmed | Noxa inhibits oncogenesis through ZNF519 in gastric cancer and is suppressed by hsa-miR-200b-3p |
| title_short | Noxa inhibits oncogenesis through ZNF519 in gastric cancer and is suppressed by hsa-miR-200b-3p |
| title_sort | noxa inhibits oncogenesis through znf519 in gastric cancer and is suppressed by hsa mir 200b 3p |
| topic | Gastric cancer Noxa Hsa-miR-200b-3p ZNF519 Prognosis Proliferation |
| url | https://doi.org/10.1038/s41598-024-57099-7 |
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