SNHG17 alters anaerobic glycolysis by resetting phosphorylation modification of PGK1 to foster pro-tumor macrophage formation in pancreatic ductal adenocarcinoma
Abstract Background Within the tumor immune microenvironment (TME), tumor-associated macrophages (TAMs) are crucial in modulating polarization states to influence cancer development through metabolic reprogramming. While long non-coding RNAs (lncRNAs) have been shown to play a pivotal role in the pr...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-12-01
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| Series: | Journal of Experimental & Clinical Cancer Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13046-023-02890-z |
| _version_ | 1797387980975898624 |
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| author | Jiayu Lin Yihao Liu Pengyi Liu Wenxin Qi Jia Liu Xingfeng He Qian Liu Zehua Liu Jingxin Yin Jiewei Lin Haili Bao Jianhong Lin |
| author_facet | Jiayu Lin Yihao Liu Pengyi Liu Wenxin Qi Jia Liu Xingfeng He Qian Liu Zehua Liu Jingxin Yin Jiewei Lin Haili Bao Jianhong Lin |
| author_sort | Jiayu Lin |
| collection | DOAJ |
| description | Abstract Background Within the tumor immune microenvironment (TME), tumor-associated macrophages (TAMs) are crucial in modulating polarization states to influence cancer development through metabolic reprogramming. While long non-coding RNAs (lncRNAs) have been shown to play a pivotal role in the progression of various cancers, the underlying mechanisms by which lncRNAs alter M2 polarization through macrophage metabolism remodeling remain unelucidated. Methods RNA sequencing was used to screen for differentially expressed lncRNAs in TAMs and normal tissue-resident macrophages (NTRMs) isolated from pancreatic ductal adenocarcinoma (PDAC) tissues, whilst RT-qPCR and FISH were employed to detect the expression level of SNHG17. Moreover, a series of in vivo and in vitro experiments were conducted to assess the functions of SNHG17 from TAMs in the polarization and glycolysis of M2-like macrophages and in the proliferation and metastasis of pancreatic cancer cells (PCs). Furthermore, Western blotting, RNA pull-down, mass spectrometry, RIP, and dual-luciferase assays were utilized to explore the underlying mechanism through which SNHG17 induces pro-tumor macrophage formation. Results SNHG17 was substantially enriched in TAMs and was positively correlated with a worse prognosis in PDAC. Meanwhile, functional assays determined that SNHG17 promoted the malignant progression of PCs by enhancing M2 macrophage polarization and anaerobic glycolysis. Mechanistically, SNHG17 could sponge miR-628-5p to release PGK1 mRNA and concurrently interact with the PGK1 protein, activating the pro-tumorigenic function of PGK1 by enhancing phosphorylation at the T168A site of PGK1 through ERK1/2 recruitment. Lastly, SNHG17 knockdown could reverse the polarization status of macrophages in PDAC. Conclusions The present study illustrated the essential role of SNHG17 and its molecular mechanism in TAMs derived from PDAC, indicating that SNHG17 might be a viable target for PDAC immunotherapy. |
| first_indexed | 2024-03-08T22:34:04Z |
| format | Article |
| id | doaj.art-21d4fa5db8804b75a478bb890a77898f |
| institution | Directory Open Access Journal |
| issn | 1756-9966 |
| language | English |
| last_indexed | 2024-03-08T22:34:04Z |
| publishDate | 2023-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Experimental & Clinical Cancer Research |
| spelling | doaj.art-21d4fa5db8804b75a478bb890a77898f2023-12-17T12:33:40ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662023-12-0142111910.1186/s13046-023-02890-zSNHG17 alters anaerobic glycolysis by resetting phosphorylation modification of PGK1 to foster pro-tumor macrophage formation in pancreatic ductal adenocarcinomaJiayu Lin0Yihao Liu1Pengyi Liu2Wenxin Qi3Jia Liu4Xingfeng He5Qian Liu6Zehua Liu7Jingxin Yin8Jiewei Lin9Haili Bao10Jianhong Lin11Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineDepartment of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineDepartment of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of MedicineDepartment of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineDepartment of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of MedicineDrug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of HelsinkiDepartment of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineResearch Institute of Pancreatic Disease, Shanghai Jiaotong University School of MedicineDepartment of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Pharmacy, The Third Hospital of XiamenAbstract Background Within the tumor immune microenvironment (TME), tumor-associated macrophages (TAMs) are crucial in modulating polarization states to influence cancer development through metabolic reprogramming. While long non-coding RNAs (lncRNAs) have been shown to play a pivotal role in the progression of various cancers, the underlying mechanisms by which lncRNAs alter M2 polarization through macrophage metabolism remodeling remain unelucidated. Methods RNA sequencing was used to screen for differentially expressed lncRNAs in TAMs and normal tissue-resident macrophages (NTRMs) isolated from pancreatic ductal adenocarcinoma (PDAC) tissues, whilst RT-qPCR and FISH were employed to detect the expression level of SNHG17. Moreover, a series of in vivo and in vitro experiments were conducted to assess the functions of SNHG17 from TAMs in the polarization and glycolysis of M2-like macrophages and in the proliferation and metastasis of pancreatic cancer cells (PCs). Furthermore, Western blotting, RNA pull-down, mass spectrometry, RIP, and dual-luciferase assays were utilized to explore the underlying mechanism through which SNHG17 induces pro-tumor macrophage formation. Results SNHG17 was substantially enriched in TAMs and was positively correlated with a worse prognosis in PDAC. Meanwhile, functional assays determined that SNHG17 promoted the malignant progression of PCs by enhancing M2 macrophage polarization and anaerobic glycolysis. Mechanistically, SNHG17 could sponge miR-628-5p to release PGK1 mRNA and concurrently interact with the PGK1 protein, activating the pro-tumorigenic function of PGK1 by enhancing phosphorylation at the T168A site of PGK1 through ERK1/2 recruitment. Lastly, SNHG17 knockdown could reverse the polarization status of macrophages in PDAC. Conclusions The present study illustrated the essential role of SNHG17 and its molecular mechanism in TAMs derived from PDAC, indicating that SNHG17 might be a viable target for PDAC immunotherapy.https://doi.org/10.1186/s13046-023-02890-zTAMsPDACSNHG17Anaerobic glycolysismiR-628-5pPGK1 |
| spellingShingle | Jiayu Lin Yihao Liu Pengyi Liu Wenxin Qi Jia Liu Xingfeng He Qian Liu Zehua Liu Jingxin Yin Jiewei Lin Haili Bao Jianhong Lin SNHG17 alters anaerobic glycolysis by resetting phosphorylation modification of PGK1 to foster pro-tumor macrophage formation in pancreatic ductal adenocarcinoma Journal of Experimental & Clinical Cancer Research TAMs PDAC SNHG17 Anaerobic glycolysis miR-628-5p PGK1 |
| title | SNHG17 alters anaerobic glycolysis by resetting phosphorylation modification of PGK1 to foster pro-tumor macrophage formation in pancreatic ductal adenocarcinoma |
| title_full | SNHG17 alters anaerobic glycolysis by resetting phosphorylation modification of PGK1 to foster pro-tumor macrophage formation in pancreatic ductal adenocarcinoma |
| title_fullStr | SNHG17 alters anaerobic glycolysis by resetting phosphorylation modification of PGK1 to foster pro-tumor macrophage formation in pancreatic ductal adenocarcinoma |
| title_full_unstemmed | SNHG17 alters anaerobic glycolysis by resetting phosphorylation modification of PGK1 to foster pro-tumor macrophage formation in pancreatic ductal adenocarcinoma |
| title_short | SNHG17 alters anaerobic glycolysis by resetting phosphorylation modification of PGK1 to foster pro-tumor macrophage formation in pancreatic ductal adenocarcinoma |
| title_sort | snhg17 alters anaerobic glycolysis by resetting phosphorylation modification of pgk1 to foster pro tumor macrophage formation in pancreatic ductal adenocarcinoma |
| topic | TAMs PDAC SNHG17 Anaerobic glycolysis miR-628-5p PGK1 |
| url | https://doi.org/10.1186/s13046-023-02890-z |
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