PYCR1 promotes the malignant progression of lung cancer through the JAK-STAT3 signaling pathway via PRODH-dependent glutamine synthesize
Background: Lung cancer is a serious threat to human life. It is of great significance to elucidate the pathogenesis of lung cancer and search for new markers. This study evaluate the clinical value of pyrroline-5-carboxylate reductase 1 (PYCR1) and explore its role and mechanisms in the malignant p...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-06-01
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| Series: | Translational Oncology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1936523323000530 |
| _version_ | 1797844329212936192 |
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| author | Lihong Zhang Xinyu Zhao Enqin Wang Ye Yang Liangfeng Hu Hongkun Xu Baojun Zhang |
| author_facet | Lihong Zhang Xinyu Zhao Enqin Wang Ye Yang Liangfeng Hu Hongkun Xu Baojun Zhang |
| author_sort | Lihong Zhang |
| collection | DOAJ |
| description | Background: Lung cancer is a serious threat to human life. It is of great significance to elucidate the pathogenesis of lung cancer and search for new markers. This study evaluate the clinical value of pyrroline-5-carboxylate reductase 1 (PYCR1) and explore its role and mechanisms in the malignant progression of lung cancer. Methods: PYCR1 expression and its relationship with prognosis were analyzed using a bioinformatics database. Enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry were utilized to examine the expression of PYCR1 in lung cancer tissues and peripheral blood. PYCR1-overexpressing lung cancer cells were constructed, then the cell proliferative, migration, and invasion ability was examined by the MTT and Transwell assays. siRNA against PRODH and STAT3 inhibitor sttatic was used to further elucidate the underlying mechanisms. Luciferase and CHIP assays were carried out for validate the how PYCR1 regulated PD-L1 expression via STAT3. Xenograft experiment was performed to determine the role of PYCR1 in vivo. Results: Database analysis showed that PYCR1 expression was significantly increased in lung cancer tissues, and its high expression predicted poor prognosis. Lung cancer tissue and peripheral blood of patients showed obviously increased PYCR1 expression, and the sensitivity and specificity of serum PYCR1 in the diagnosis of lung cancer were 75.7% and 60%, respectively. PYCR1 overexpression enhanced the proliferative, migration, and invasion abilities of lung cancer cells. Both PRODH silence and stattic effectively attenuated the function of PYCR1. Animal experiment and IHC data indicated that PYCR1 could activated STAT3 phosphorylation and PD-L1, as well as suppressed T cell infiltration in lung cancer. Finally, we also validated that PYCR1 promoted PD-L1 transcription by elevating STAT3 binding to the gene promoter. Conclusion: PYCR1 has certain value in the diagnosis and prognosis of lung cancer. Moreover, through regulating JAK-STAT3 signaling pathway, PYCR1 significantly participated in process of lung cancer progression via the metabolism link between proline and glutamine, indicating that PYCR1 might be also a novel therapeutic target. |
| first_indexed | 2024-04-09T17:20:32Z |
| format | Article |
| id | doaj.art-7155a601ec8c4e6298025cbcd60de91e |
| institution | Directory Open Access Journal |
| issn | 1936-5233 |
| language | English |
| last_indexed | 2024-04-09T17:20:32Z |
| publishDate | 2023-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Translational Oncology |
| spelling | doaj.art-7155a601ec8c4e6298025cbcd60de91e2023-04-19T04:22:19ZengElsevierTranslational Oncology1936-52332023-06-0132101667PYCR1 promotes the malignant progression of lung cancer through the JAK-STAT3 signaling pathway via PRODH-dependent glutamine synthesizeLihong Zhang0Xinyu Zhao1Enqin Wang2Ye Yang3Liangfeng Hu4Hongkun Xu5Baojun Zhang6Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University, No. 76, Yanta West Road, Xi'an, Shanxi, ChinaDepartment of Clinical Laboratory Center, Shaoxing People's Hospital, Shaoxing, ChinaDepartment of Clinical Laboratory Center, Shaoxing People's Hospital, Shaoxing, ChinaDepartment of Pathology, Shaoxing People's Hospital, Shaoxing, ChinaDepartment of Clinical Laboratory Center, Shaoxing People's Hospital, Shaoxing, ChinaDepartment of Clinical Laboratory Center, Shaoxing People's Hospital, Shaoxing, ChinaDepartment of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University, No. 76, Yanta West Road, Xi'an, Shanxi, China; Corresponding author.Background: Lung cancer is a serious threat to human life. It is of great significance to elucidate the pathogenesis of lung cancer and search for new markers. This study evaluate the clinical value of pyrroline-5-carboxylate reductase 1 (PYCR1) and explore its role and mechanisms in the malignant progression of lung cancer. Methods: PYCR1 expression and its relationship with prognosis were analyzed using a bioinformatics database. Enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry were utilized to examine the expression of PYCR1 in lung cancer tissues and peripheral blood. PYCR1-overexpressing lung cancer cells were constructed, then the cell proliferative, migration, and invasion ability was examined by the MTT and Transwell assays. siRNA against PRODH and STAT3 inhibitor sttatic was used to further elucidate the underlying mechanisms. Luciferase and CHIP assays were carried out for validate the how PYCR1 regulated PD-L1 expression via STAT3. Xenograft experiment was performed to determine the role of PYCR1 in vivo. Results: Database analysis showed that PYCR1 expression was significantly increased in lung cancer tissues, and its high expression predicted poor prognosis. Lung cancer tissue and peripheral blood of patients showed obviously increased PYCR1 expression, and the sensitivity and specificity of serum PYCR1 in the diagnosis of lung cancer were 75.7% and 60%, respectively. PYCR1 overexpression enhanced the proliferative, migration, and invasion abilities of lung cancer cells. Both PRODH silence and stattic effectively attenuated the function of PYCR1. Animal experiment and IHC data indicated that PYCR1 could activated STAT3 phosphorylation and PD-L1, as well as suppressed T cell infiltration in lung cancer. Finally, we also validated that PYCR1 promoted PD-L1 transcription by elevating STAT3 binding to the gene promoter. Conclusion: PYCR1 has certain value in the diagnosis and prognosis of lung cancer. Moreover, through regulating JAK-STAT3 signaling pathway, PYCR1 significantly participated in process of lung cancer progression via the metabolism link between proline and glutamine, indicating that PYCR1 might be also a novel therapeutic target.http://www.sciencedirect.com/science/article/pii/S1936523323000530PYCR1JAK-STAT3PRODHGlutaminePD-L1 |
| spellingShingle | Lihong Zhang Xinyu Zhao Enqin Wang Ye Yang Liangfeng Hu Hongkun Xu Baojun Zhang PYCR1 promotes the malignant progression of lung cancer through the JAK-STAT3 signaling pathway via PRODH-dependent glutamine synthesize Translational Oncology PYCR1 JAK-STAT3 PRODH Glutamine PD-L1 |
| title | PYCR1 promotes the malignant progression of lung cancer through the JAK-STAT3 signaling pathway via PRODH-dependent glutamine synthesize |
| title_full | PYCR1 promotes the malignant progression of lung cancer through the JAK-STAT3 signaling pathway via PRODH-dependent glutamine synthesize |
| title_fullStr | PYCR1 promotes the malignant progression of lung cancer through the JAK-STAT3 signaling pathway via PRODH-dependent glutamine synthesize |
| title_full_unstemmed | PYCR1 promotes the malignant progression of lung cancer through the JAK-STAT3 signaling pathway via PRODH-dependent glutamine synthesize |
| title_short | PYCR1 promotes the malignant progression of lung cancer through the JAK-STAT3 signaling pathway via PRODH-dependent glutamine synthesize |
| title_sort | pycr1 promotes the malignant progression of lung cancer through the jak stat3 signaling pathway via prodh dependent glutamine synthesize |
| topic | PYCR1 JAK-STAT3 PRODH Glutamine PD-L1 |
| url | http://www.sciencedirect.com/science/article/pii/S1936523323000530 |
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