PUM1 Promotes Tumor Progression by Activating DEPTOR‐Meditated Glycolysis in Gastric Cancer
Abstract RNA‐binding proteins (RBPs) play essential roles in tumorigenesis and progression, but their functions in gastric cancer (GC) remain largely elusive. Here, it is reported that Pumilio 1 (PUM1), an RBP, induces metabolic reprogramming through post‐transcriptional regulation of DEP domain‐con...
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| Format: | Article |
| Language: | English |
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Wiley
2023-09-01
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| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202301190 |
| _version_ | 1797674017475264512 |
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| author | Songcheng Yin Huifang Liu Zhijun Zhou Xiaoyu Xu Pengliang Wang Wei Chen Guofei Deng Han Wang Hong Yu Liang Gu Mingyu Huo Min Li Leli Zeng Yulong He Changhua Zhang |
| author_facet | Songcheng Yin Huifang Liu Zhijun Zhou Xiaoyu Xu Pengliang Wang Wei Chen Guofei Deng Han Wang Hong Yu Liang Gu Mingyu Huo Min Li Leli Zeng Yulong He Changhua Zhang |
| author_sort | Songcheng Yin |
| collection | DOAJ |
| description | Abstract RNA‐binding proteins (RBPs) play essential roles in tumorigenesis and progression, but their functions in gastric cancer (GC) remain largely elusive. Here, it is reported that Pumilio 1 (PUM1), an RBP, induces metabolic reprogramming through post‐transcriptional regulation of DEP domain‐containing mammalian target of rapamycin (mTOR)‐interacting protein (DEPTOR) in GC. In clinical samples, elevated expression of PUM1 is associated with recurrence, metastasis, and poor survival. In vitro and in vivo experiments demonstrate that knockdown of PUM1 inhibits the proliferation and metastasis of GC cells. In addition, RNA‐sequencing and bioinformatics analyses show that PUM1 is enriched in the glycolysis gene signature. Metabolomics studies confirm that PUM1 deficiency suppresses glycolytic metabolism. Mechanistically, PUM1 binds directly to DEPTOR mRNA pumilio response element to maintain the stability of the transcript and prevent DEPTOR degradation through post‐transcriptional pathway. PUM1‐mediated DEPTOR upregulation inhibits mTORC1 and alleviates the inhibitory feedback signal transmitted from mTORC1 to PI3K under normal conditions, thus activating the PI3K–Akt signal and glycolysis continuously. Collectively, these results reveal the critical epigenetic role of PUM1 in modulating DEPTOR‐dependent GC progression. These conclusions support further clinical investigation of PUM1 inhibitors as a metabolic‐targeting treatment strategy for GC. |
| first_indexed | 2024-03-11T21:53:02Z |
| format | Article |
| id | doaj.art-cf42e30bcbeb46edaea6e23f7eb5d8dd |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-03-11T21:53:02Z |
| publishDate | 2023-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-cf42e30bcbeb46edaea6e23f7eb5d8dd2023-09-26T07:39:32ZengWileyAdvanced Science2198-38442023-09-011027n/an/a10.1002/advs.202301190PUM1 Promotes Tumor Progression by Activating DEPTOR‐Meditated Glycolysis in Gastric CancerSongcheng Yin0Huifang Liu1Zhijun Zhou2Xiaoyu Xu3Pengliang Wang4Wei Chen5Guofei Deng6Han Wang7Hong Yu8Liang Gu9Mingyu Huo10Min Li11Leli Zeng12Yulong He13Changhua Zhang14Digestive Diseases Center Guangdong Provincial Key Laboratory of Digestive Cancer Research The Seventh Affiliated Hospital of Sun Yat‐sen University Shenzhen Guangdong 518107 ChinaDigestive Diseases Center Guangdong Provincial Key Laboratory of Digestive Cancer Research The Seventh Affiliated Hospital of Sun Yat‐sen University Shenzhen Guangdong 518107 ChinaDepartment of Medicine The University of Oklahoma Health Sciences Center Oklahoma City OK 73104 USADepartment of Gynecology and Obstetrics The Seventh Affiliated Hospital of Sun Yat‐sen University Shenzhen Guangdong 518107 ChinaDepartment of Gastrointestinal Surgery Sun Yat‐sen Memorial Hospital Sun Yat‐sen University Guangzhou Guangdong 510120 ChinaDigestive Diseases Center Guangdong Provincial Key Laboratory of Digestive Cancer Research The Seventh Affiliated Hospital of Sun Yat‐sen University Shenzhen Guangdong 518107 ChinaDigestive Diseases Center Guangdong Provincial Key Laboratory of Digestive Cancer Research The Seventh Affiliated Hospital of Sun Yat‐sen University Shenzhen Guangdong 518107 ChinaDigestive Diseases Center Guangdong Provincial Key Laboratory of Digestive Cancer Research The Seventh Affiliated Hospital of Sun Yat‐sen University Shenzhen Guangdong 518107 ChinaDigestive Diseases Center Guangdong Provincial Key Laboratory of Digestive Cancer Research The Seventh Affiliated Hospital of Sun Yat‐sen University Shenzhen Guangdong 518107 ChinaDigestive Diseases Center Guangdong Provincial Key Laboratory of Digestive Cancer Research The Seventh Affiliated Hospital of Sun Yat‐sen University Shenzhen Guangdong 518107 ChinaDigestive Diseases Center Guangdong Provincial Key Laboratory of Digestive Cancer Research The Seventh Affiliated Hospital of Sun Yat‐sen University Shenzhen Guangdong 518107 ChinaDepartment of Medicine The University of Oklahoma Health Sciences Center Oklahoma City OK 73104 USADigestive Diseases Center Guangdong Provincial Key Laboratory of Digestive Cancer Research The Seventh Affiliated Hospital of Sun Yat‐sen University Shenzhen Guangdong 518107 ChinaDigestive Diseases Center Guangdong Provincial Key Laboratory of Digestive Cancer Research The Seventh Affiliated Hospital of Sun Yat‐sen University Shenzhen Guangdong 518107 ChinaDigestive Diseases Center Guangdong Provincial Key Laboratory of Digestive Cancer Research The Seventh Affiliated Hospital of Sun Yat‐sen University Shenzhen Guangdong 518107 ChinaAbstract RNA‐binding proteins (RBPs) play essential roles in tumorigenesis and progression, but their functions in gastric cancer (GC) remain largely elusive. Here, it is reported that Pumilio 1 (PUM1), an RBP, induces metabolic reprogramming through post‐transcriptional regulation of DEP domain‐containing mammalian target of rapamycin (mTOR)‐interacting protein (DEPTOR) in GC. In clinical samples, elevated expression of PUM1 is associated with recurrence, metastasis, and poor survival. In vitro and in vivo experiments demonstrate that knockdown of PUM1 inhibits the proliferation and metastasis of GC cells. In addition, RNA‐sequencing and bioinformatics analyses show that PUM1 is enriched in the glycolysis gene signature. Metabolomics studies confirm that PUM1 deficiency suppresses glycolytic metabolism. Mechanistically, PUM1 binds directly to DEPTOR mRNA pumilio response element to maintain the stability of the transcript and prevent DEPTOR degradation through post‐transcriptional pathway. PUM1‐mediated DEPTOR upregulation inhibits mTORC1 and alleviates the inhibitory feedback signal transmitted from mTORC1 to PI3K under normal conditions, thus activating the PI3K–Akt signal and glycolysis continuously. Collectively, these results reveal the critical epigenetic role of PUM1 in modulating DEPTOR‐dependent GC progression. These conclusions support further clinical investigation of PUM1 inhibitors as a metabolic‐targeting treatment strategy for GC.https://doi.org/10.1002/advs.202301190DEPTORgastric cancerglycolysisPI3K–Akt pathwayPUM1 |
| spellingShingle | Songcheng Yin Huifang Liu Zhijun Zhou Xiaoyu Xu Pengliang Wang Wei Chen Guofei Deng Han Wang Hong Yu Liang Gu Mingyu Huo Min Li Leli Zeng Yulong He Changhua Zhang PUM1 Promotes Tumor Progression by Activating DEPTOR‐Meditated Glycolysis in Gastric Cancer Advanced Science DEPTOR gastric cancer glycolysis PI3K–Akt pathway PUM1 |
| title | PUM1 Promotes Tumor Progression by Activating DEPTOR‐Meditated Glycolysis in Gastric Cancer |
| title_full | PUM1 Promotes Tumor Progression by Activating DEPTOR‐Meditated Glycolysis in Gastric Cancer |
| title_fullStr | PUM1 Promotes Tumor Progression by Activating DEPTOR‐Meditated Glycolysis in Gastric Cancer |
| title_full_unstemmed | PUM1 Promotes Tumor Progression by Activating DEPTOR‐Meditated Glycolysis in Gastric Cancer |
| title_short | PUM1 Promotes Tumor Progression by Activating DEPTOR‐Meditated Glycolysis in Gastric Cancer |
| title_sort | pum1 promotes tumor progression by activating deptor meditated glycolysis in gastric cancer |
| topic | DEPTOR gastric cancer glycolysis PI3K–Akt pathway PUM1 |
| url | https://doi.org/10.1002/advs.202301190 |
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