Transmembrane protein 176B regulates amino acid metabolism through the PI3K-Akt-mTOR signaling pathway and promotes gastric cancer progression
Abstract Background The present study aimed to investigate the expression level, biological function, and underlying mechanism of transmembrane protein 176B (TMEM176B) in gastric cancer (GC). Methods TMEM176B expression was detected by quantitative real-time polymerase chain reaction (qRT-PCR) and w...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2024-03-01
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| Series: | Cancer Cell International |
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| Online Access: | https://doi.org/10.1186/s12935-024-03279-4 |
| _version_ | 1797273179255734272 |
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| author | Jing Li ZiQing Fang Emre Dal Hao Zhang KeXun Yu MengDi Ma MingLiang Wang Ruochuan Sun MingDian Lu HuiZhen Wang YongXiang Li |
| author_facet | Jing Li ZiQing Fang Emre Dal Hao Zhang KeXun Yu MengDi Ma MingLiang Wang Ruochuan Sun MingDian Lu HuiZhen Wang YongXiang Li |
| author_sort | Jing Li |
| collection | DOAJ |
| description | Abstract Background The present study aimed to investigate the expression level, biological function, and underlying mechanism of transmembrane protein 176B (TMEM176B) in gastric cancer (GC). Methods TMEM176B expression was detected by quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting (WB). The function of TMEM176B was determined by various in vitro assays including colony formation, 5-ethynyl-2ʹ-deoxyuridine (EdU), Transwell, and flow cytometry. Bioinformatics techniques were then used to elucidate the signaling pathways associated with TMEM176B activity. Tumor formation experiments were conducted on nude mice for in vivo validation of the preceding findings. TMEM176B expression was cross-referenced to clinicopathological parameters and survival outcomes. Results It was observed that TMEM176B was overexpressed in GC cells and tissues. Targeted TMEM176B abrogation inhibited colony formation, proliferation, migration, and invasion but promoted apoptosis in GC cell lines while TMEM176B overexpression had the opposite effects. Subsequent experimental validation disclosed an association between TMEM176B and the phosphatidylinositol 3-carboxykinase (PI3K)-protein kinase B (Akt)-mammalian target of rapamycin (mTOR) signaling axis. Moreover, TMEM176B affects GC cancer progression by regulating asparagine synthetase (ASNS). The in vivo assays confirmed that TMEM176B is oncogenic and the clinical data revealed a connection between TMEM176B expression and the clinicopathological determinants of GC. Conclusion The foregoing results suggest that TMEM176B significantly promotes the development of gastric cancer and is an independent prognostic factor of it. |
| first_indexed | 2024-03-07T14:39:54Z |
| format | Article |
| id | doaj.art-912c0935105c4ebcaa85505291b75484 |
| institution | Directory Open Access Journal |
| issn | 1475-2867 |
| language | English |
| last_indexed | 2024-03-07T14:39:54Z |
| publishDate | 2024-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj.art-912c0935105c4ebcaa85505291b754842024-03-05T20:25:26ZengBMCCancer Cell International1475-28672024-03-0124111510.1186/s12935-024-03279-4Transmembrane protein 176B regulates amino acid metabolism through the PI3K-Akt-mTOR signaling pathway and promotes gastric cancer progressionJing Li0ZiQing Fang1Emre Dal2Hao Zhang3KeXun Yu4MengDi Ma5MingLiang Wang6Ruochuan Sun7MingDian Lu8HuiZhen Wang9YongXiang Li10Department of General Surgery, The First Affiliated Hospital of Anhui Medical UniversityDepartment of General Surgery, The First Affiliated Hospital of Anhui Medical UniversityUniversity of UtahDepartment of General Surgery, The First Affiliated Hospital of Anhui Medical UniversityDepartment of General Surgery, The First Affiliated Hospital of Anhui Medical UniversityDepartment of General Surgery, The First Affiliated Hospital of Anhui Medical UniversityDepartment of General Surgery, The First Affiliated Hospital of Anhui Medical UniversityDepartment of General Surgery, The First Affiliated Hospital of Anhui Medical UniversityDepartment of General Surgery, The First Affiliated Hospital of Anhui Medical UniversityDepartment of General Surgery, The First Affiliated Hospital of Anhui Medical UniversityDepartment of General Surgery, The First Affiliated Hospital of Anhui Medical UniversityAbstract Background The present study aimed to investigate the expression level, biological function, and underlying mechanism of transmembrane protein 176B (TMEM176B) in gastric cancer (GC). Methods TMEM176B expression was detected by quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting (WB). The function of TMEM176B was determined by various in vitro assays including colony formation, 5-ethynyl-2ʹ-deoxyuridine (EdU), Transwell, and flow cytometry. Bioinformatics techniques were then used to elucidate the signaling pathways associated with TMEM176B activity. Tumor formation experiments were conducted on nude mice for in vivo validation of the preceding findings. TMEM176B expression was cross-referenced to clinicopathological parameters and survival outcomes. Results It was observed that TMEM176B was overexpressed in GC cells and tissues. Targeted TMEM176B abrogation inhibited colony formation, proliferation, migration, and invasion but promoted apoptosis in GC cell lines while TMEM176B overexpression had the opposite effects. Subsequent experimental validation disclosed an association between TMEM176B and the phosphatidylinositol 3-carboxykinase (PI3K)-protein kinase B (Akt)-mammalian target of rapamycin (mTOR) signaling axis. Moreover, TMEM176B affects GC cancer progression by regulating asparagine synthetase (ASNS). The in vivo assays confirmed that TMEM176B is oncogenic and the clinical data revealed a connection between TMEM176B expression and the clinicopathological determinants of GC. Conclusion The foregoing results suggest that TMEM176B significantly promotes the development of gastric cancer and is an independent prognostic factor of it.https://doi.org/10.1186/s12935-024-03279-4Asparagine synthetaseGastric cancerMammalian target of rapamycinPhosphoinositide 3-kinaseProtein kinase BTransmembrane protein 176B |
| spellingShingle | Jing Li ZiQing Fang Emre Dal Hao Zhang KeXun Yu MengDi Ma MingLiang Wang Ruochuan Sun MingDian Lu HuiZhen Wang YongXiang Li Transmembrane protein 176B regulates amino acid metabolism through the PI3K-Akt-mTOR signaling pathway and promotes gastric cancer progression Cancer Cell International Asparagine synthetase Gastric cancer Mammalian target of rapamycin Phosphoinositide 3-kinase Protein kinase B Transmembrane protein 176B |
| title | Transmembrane protein 176B regulates amino acid metabolism through the PI3K-Akt-mTOR signaling pathway and promotes gastric cancer progression |
| title_full | Transmembrane protein 176B regulates amino acid metabolism through the PI3K-Akt-mTOR signaling pathway and promotes gastric cancer progression |
| title_fullStr | Transmembrane protein 176B regulates amino acid metabolism through the PI3K-Akt-mTOR signaling pathway and promotes gastric cancer progression |
| title_full_unstemmed | Transmembrane protein 176B regulates amino acid metabolism through the PI3K-Akt-mTOR signaling pathway and promotes gastric cancer progression |
| title_short | Transmembrane protein 176B regulates amino acid metabolism through the PI3K-Akt-mTOR signaling pathway and promotes gastric cancer progression |
| title_sort | transmembrane protein 176b regulates amino acid metabolism through the pi3k akt mtor signaling pathway and promotes gastric cancer progression |
| topic | Asparagine synthetase Gastric cancer Mammalian target of rapamycin Phosphoinositide 3-kinase Protein kinase B Transmembrane protein 176B |
| url | https://doi.org/10.1186/s12935-024-03279-4 |
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