Abstract
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.