{"title":"PTPMT1抑制通过破坏线粒体代谢诱导人SCLC细胞凋亡和生长停滞。","authors":"Xiang Liu, Yang Sun, Chuancheng Gao, Huiyan Sun, Fang Tian, Fengjun Xiao, Qinqin Xu","doi":"10.21037/tcr-2024-2379","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Many cancer cells exhibit aberrant metabolic reprogramming through abnormal mitochondrial respiration. Protein tyrosine phosphatase mitochondrial 1 (PTPMT1) is a protein tyrosine phosphatase localized to the mitochondria and linked to mitochondrial respiration. However, the expression and role of PTPMT1 in regulating the biological characteristics of small cell lung cancer (SCLC) has not yet been explored. The aim of this study was to evaluate the role of PTPMT1 on SCLC cell survival and mitochondrial function.</p><p><strong>Methods: </strong>SCLC and adjacent normal tissues were obtained from surgery. The expression level of PTPMT1 in the SCLC tissues and cell lines was determined by immunohistochemical staining, western blot, and quantitative real-time polymerase chain reaction (qRT-PCR). PTPMT1 knockdown was induced by lentivirus-mediated short-hairpin RNA (shRNA) transduction and PTPMT1 inhibition (alexidine dihydrochloride). The biological characteristics of the cells were measured by cell counting kit 8 (CCK-8), colony formation assay, and cell migration assay. The mitochondrial function of the cells was measured by 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolylcarbocyanine iodide (JC-1) staining. The H69 cells were treated with alexidine dihydrochloride, after which transcriptome sequencing and an untargeted metabolomic analysis were performed. The transcriptome differentially expressed genes were measured by qRT-PCR.</p><p><strong>Results: </strong>PTPMT1 was upregulated in the SCLC tissues compared to the adjacent normal tissues. PTPMT1 inhibition by lentiviral shRNA transduction or specific inhibition resulted in significant growth arrest and apoptosis. The transcriptome sequencing analysis revealed that pathways related to the respiration chain and mitochondrial member protein were disrupted. Several mitochondrial metabolism-related genes, such as <i>FGF21</i>, <i>GDF-15</i>, <i>APLN</i>, and <i>MT-DN6</i>, were dysregulated. Further, PTPMT1 inhibition was found to downregulate Glut expression and disturb mitochondrial function.</p><p><strong>Conclusions: </strong>PTPMT1 was shown to play a critical role in the survival and growth of SCLC cells, and may become a potential therapeutic target.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"13 12","pages":"6956-6969"},"PeriodicalIF":1.5000,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11730198/pdf/","citationCount":"0","resultStr":"{\"title\":\"PTPMT1 inhibition induces apoptosis and growth arrest of human SCLC cells by disrupting mitochondrial metabolism.\",\"authors\":\"Xiang Liu, Yang Sun, Chuancheng Gao, Huiyan Sun, Fang Tian, Fengjun Xiao, Qinqin Xu\",\"doi\":\"10.21037/tcr-2024-2379\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Many cancer cells exhibit aberrant metabolic reprogramming through abnormal mitochondrial respiration. Protein tyrosine phosphatase mitochondrial 1 (PTPMT1) is a protein tyrosine phosphatase localized to the mitochondria and linked to mitochondrial respiration. However, the expression and role of PTPMT1 in regulating the biological characteristics of small cell lung cancer (SCLC) has not yet been explored. The aim of this study was to evaluate the role of PTPMT1 on SCLC cell survival and mitochondrial function.</p><p><strong>Methods: </strong>SCLC and adjacent normal tissues were obtained from surgery. The expression level of PTPMT1 in the SCLC tissues and cell lines was determined by immunohistochemical staining, western blot, and quantitative real-time polymerase chain reaction (qRT-PCR). PTPMT1 knockdown was induced by lentivirus-mediated short-hairpin RNA (shRNA) transduction and PTPMT1 inhibition (alexidine dihydrochloride). The biological characteristics of the cells were measured by cell counting kit 8 (CCK-8), colony formation assay, and cell migration assay. The mitochondrial function of the cells was measured by 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolylcarbocyanine iodide (JC-1) staining. The H69 cells were treated with alexidine dihydrochloride, after which transcriptome sequencing and an untargeted metabolomic analysis were performed. The transcriptome differentially expressed genes were measured by qRT-PCR.</p><p><strong>Results: </strong>PTPMT1 was upregulated in the SCLC tissues compared to the adjacent normal tissues. PTPMT1 inhibition by lentiviral shRNA transduction or specific inhibition resulted in significant growth arrest and apoptosis. The transcriptome sequencing analysis revealed that pathways related to the respiration chain and mitochondrial member protein were disrupted. Several mitochondrial metabolism-related genes, such as <i>FGF21</i>, <i>GDF-15</i>, <i>APLN</i>, and <i>MT-DN6</i>, were dysregulated. Further, PTPMT1 inhibition was found to downregulate Glut expression and disturb mitochondrial function.</p><p><strong>Conclusions: </strong>PTPMT1 was shown to play a critical role in the survival and growth of SCLC cells, and may become a potential therapeutic target.</p>\",\"PeriodicalId\":23216,\"journal\":{\"name\":\"Translational cancer research\",\"volume\":\"13 12\",\"pages\":\"6956-6969\"},\"PeriodicalIF\":1.5000,\"publicationDate\":\"2024-12-31\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11730198/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Translational cancer research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.21037/tcr-2024-2379\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/12/27 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q4\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Translational cancer research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.21037/tcr-2024-2379","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/12/27 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"ONCOLOGY","Score":null,"Total":0}
PTPMT1 inhibition induces apoptosis and growth arrest of human SCLC cells by disrupting mitochondrial metabolism.
Background: Many cancer cells exhibit aberrant metabolic reprogramming through abnormal mitochondrial respiration. Protein tyrosine phosphatase mitochondrial 1 (PTPMT1) is a protein tyrosine phosphatase localized to the mitochondria and linked to mitochondrial respiration. However, the expression and role of PTPMT1 in regulating the biological characteristics of small cell lung cancer (SCLC) has not yet been explored. The aim of this study was to evaluate the role of PTPMT1 on SCLC cell survival and mitochondrial function.
Methods: SCLC and adjacent normal tissues were obtained from surgery. The expression level of PTPMT1 in the SCLC tissues and cell lines was determined by immunohistochemical staining, western blot, and quantitative real-time polymerase chain reaction (qRT-PCR). PTPMT1 knockdown was induced by lentivirus-mediated short-hairpin RNA (shRNA) transduction and PTPMT1 inhibition (alexidine dihydrochloride). The biological characteristics of the cells were measured by cell counting kit 8 (CCK-8), colony formation assay, and cell migration assay. The mitochondrial function of the cells was measured by 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolylcarbocyanine iodide (JC-1) staining. The H69 cells were treated with alexidine dihydrochloride, after which transcriptome sequencing and an untargeted metabolomic analysis were performed. The transcriptome differentially expressed genes were measured by qRT-PCR.
Results: PTPMT1 was upregulated in the SCLC tissues compared to the adjacent normal tissues. PTPMT1 inhibition by lentiviral shRNA transduction or specific inhibition resulted in significant growth arrest and apoptosis. The transcriptome sequencing analysis revealed that pathways related to the respiration chain and mitochondrial member protein were disrupted. Several mitochondrial metabolism-related genes, such as FGF21, GDF-15, APLN, and MT-DN6, were dysregulated. Further, PTPMT1 inhibition was found to downregulate Glut expression and disturb mitochondrial function.
Conclusions: PTPMT1 was shown to play a critical role in the survival and growth of SCLC cells, and may become a potential therapeutic target.
期刊介绍：
Translational Cancer Research (Transl Cancer Res TCR; Print ISSN: 2218-676X; Online ISSN 2219-6803; http://tcr.amegroups.com/) is an Open Access, peer-reviewed journal, indexed in Science Citation Index Expanded (SCIE). TCR publishes laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer; results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of cancer patients. The focus of TCR is original, peer-reviewed, science-based research that successfully advances clinical medicine toward the goal of improving patients'' quality of life. The editors and an international advisory group of scientists and clinician-scientists as well as other experts will hold TCR articles to the high-quality standards. We accept Original Articles as well as Review Articles, Editorials and Brief Articles.
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