Circular RNA P4HB promotes glycolysis and tumor progression by binding with PKM2 in lung adenocarcinoma
Abstract Background Emerging evidence indicates that circular RNAs (circRNAs) play vital roles in tumor progression, including lung adenocarcinomas (LUAD). However, the mechanisms by which circRNAs promote the progression of LUAD still require further investigation. Methods Quantitative real-time PC...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-10-01
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| Series: | Respiratory Research |
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| Online Access: | https://doi.org/10.1186/s12931-023-02563-7 |
| _version_ | 1797451789149143040 |
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| author | Haoran Li Haifa Guo Qi Huang Shaodong Wang Xiao Li Mantang Qiu |
| author_facet | Haoran Li Haifa Guo Qi Huang Shaodong Wang Xiao Li Mantang Qiu |
| author_sort | Haoran Li |
| collection | DOAJ |
| description | Abstract Background Emerging evidence indicates that circular RNAs (circRNAs) play vital roles in tumor progression, including lung adenocarcinomas (LUAD). However, the mechanisms by which circRNAs promote the progression of LUAD still require further investigation. Methods Quantitative real-time PCR was performed to detect the expression of circP4HB in LUAD tissues and cells. Then, Kaplan–Meier analysis was used to determine the prognostic value of circP4HB expression. We employed RNA pull-down, RNA immunoprecipitation, mass spectrometry, cells fraction, glucose consumption, lactate production, pyruvate kinase M2 (PKM2) activity, and macrophage polarization assays to uncover the underlying mechanisms of circP4HB in LUAD. Results We found that circP4HB is upregulated in LUAD tissues and correlated with advanced TNM stages and lymph node metastasis. LUAD patients with high circP4HB expression had poor prognoses. Functionally, circP4HB promoted LUAD progression in vivo and in vitro. Upregulated circP4HB increased glucose consumption, lactate production and accelerated aerobic glycolysis in LUAD cells. Mechanically, circP4HB mainly accumulated in the cytoplasm of LUAD cells and bound with PKM2 and subsequently upregulating PKM2 enzymatic activity by increasing its tetramer formation. Additionally, circP4HB promoted M2 macrophage phenotype shift via targeting PKM2. Finally, rescue assays further confirmed that circP4HB could promote LUAD cell progression through its interaction with PKM2. Conclusion These results demonstrate that circP4HB could promote LUAD progression, indicating circP4HB might be a potential therapeutic target of LUAD. Graphical Abstract |
| first_indexed | 2024-03-09T14:59:28Z |
| format | Article |
| id | doaj.art-d3413c56d4bc4c4fac6528788a50459e |
| institution | Directory Open Access Journal |
| issn | 1465-993X |
| language | English |
| last_indexed | 2024-03-09T14:59:28Z |
| publishDate | 2023-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Respiratory Research |
| spelling | doaj.art-d3413c56d4bc4c4fac6528788a50459e2023-11-26T14:01:51ZengBMCRespiratory Research1465-993X2023-10-0124111610.1186/s12931-023-02563-7Circular RNA P4HB promotes glycolysis and tumor progression by binding with PKM2 in lung adenocarcinomaHaoran Li0Haifa Guo1Qi Huang2Shaodong Wang3Xiao Li4Mantang Qiu5Department of Thoracic Surgery, Peking University People’s HospitalThe First Department of Thoracic Surgery, Beijing Chest Hospital, Capital Medical UniversityDepartment of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Thoracic Surgery, Peking University People’s HospitalDepartment of Thoracic Surgery, Peking University People’s HospitalDepartment of Thoracic Surgery, Peking University People’s HospitalAbstract Background Emerging evidence indicates that circular RNAs (circRNAs) play vital roles in tumor progression, including lung adenocarcinomas (LUAD). However, the mechanisms by which circRNAs promote the progression of LUAD still require further investigation. Methods Quantitative real-time PCR was performed to detect the expression of circP4HB in LUAD tissues and cells. Then, Kaplan–Meier analysis was used to determine the prognostic value of circP4HB expression. We employed RNA pull-down, RNA immunoprecipitation, mass spectrometry, cells fraction, glucose consumption, lactate production, pyruvate kinase M2 (PKM2) activity, and macrophage polarization assays to uncover the underlying mechanisms of circP4HB in LUAD. Results We found that circP4HB is upregulated in LUAD tissues and correlated with advanced TNM stages and lymph node metastasis. LUAD patients with high circP4HB expression had poor prognoses. Functionally, circP4HB promoted LUAD progression in vivo and in vitro. Upregulated circP4HB increased glucose consumption, lactate production and accelerated aerobic glycolysis in LUAD cells. Mechanically, circP4HB mainly accumulated in the cytoplasm of LUAD cells and bound with PKM2 and subsequently upregulating PKM2 enzymatic activity by increasing its tetramer formation. Additionally, circP4HB promoted M2 macrophage phenotype shift via targeting PKM2. Finally, rescue assays further confirmed that circP4HB could promote LUAD cell progression through its interaction with PKM2. Conclusion These results demonstrate that circP4HB could promote LUAD progression, indicating circP4HB might be a potential therapeutic target of LUAD. Graphical Abstracthttps://doi.org/10.1186/s12931-023-02563-7Lung adenocarcinomacircP4HBPKM2Macrophage polarizationAerobic glycolysisPrognosis |
| spellingShingle | Haoran Li Haifa Guo Qi Huang Shaodong Wang Xiao Li Mantang Qiu Circular RNA P4HB promotes glycolysis and tumor progression by binding with PKM2 in lung adenocarcinoma Respiratory Research Lung adenocarcinoma circP4HB PKM2 Macrophage polarization Aerobic glycolysis Prognosis |
| title | Circular RNA P4HB promotes glycolysis and tumor progression by binding with PKM2 in lung adenocarcinoma |
| title_full | Circular RNA P4HB promotes glycolysis and tumor progression by binding with PKM2 in lung adenocarcinoma |
| title_fullStr | Circular RNA P4HB promotes glycolysis and tumor progression by binding with PKM2 in lung adenocarcinoma |
| title_full_unstemmed | Circular RNA P4HB promotes glycolysis and tumor progression by binding with PKM2 in lung adenocarcinoma |
| title_short | Circular RNA P4HB promotes glycolysis and tumor progression by binding with PKM2 in lung adenocarcinoma |
| title_sort | circular rna p4hb promotes glycolysis and tumor progression by binding with pkm2 in lung adenocarcinoma |
| topic | Lung adenocarcinoma circP4HB PKM2 Macrophage polarization Aerobic glycolysis Prognosis |
| url | https://doi.org/10.1186/s12931-023-02563-7 |
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