RESUMO
Purpose Patients diagnosed with cancer often suffer from emotional stressors, such as anxiety, depression, and fear of death. However, whether fear stress could influence the glioma progression is still unclear. Methods Xenograft glioma animal models were established in nude mice. Tumor-bearing mice were subjected to fear stress by living closely with cats and then their depressive behaviors were measured using an open field test. Hematoxylin and eosin staining, the TUNEL staining and immunochemical staining were used to detect the histopathological changes of tumor tissues. Gene expression profiling was used to screen the aberrant gene expression. Methylated RNA immunoprecipitation was used to identify the RNA m6A level. Gene expression was measured by western blot and real-time PCR, respectively. Results We found that fear stress promoted glioma tumor progression in mice. Fear stress-induced upregulation of METTL3 and FSP1, increased m6A level of glioma tumor tissues, and inhibited ferroptosis in glioma progression, which were reversed by knockdown of METTL3 and FSP1 in vivo. In addition, we found that when iFSP1 (a ferroptosis inducer by targeting inhibition of FSP1) was introduced to glioma cells, the cells viability of glioma significantly was decreased and ferroptosis was enhanced in glioma cells. Conclusions Fear stress-induced upregulation of METTL3 stabilized FSP1 mRNA by m6A modification, leading to tumor progression through inhibition of ferroptosis. Our study provides a new understanding of psychological effects on glioma development, and new insights for glioma therapy (AU)
Assuntos
Humanos , Camundongos , Depressão , Medo/fisiologia , Medo/psicologia , Glioma/genética , Glioma/psicologia , Estresse Psicológico/genética , Estresse Psicológico/psicologia , Modelos Animais de Doenças , Linhagem Celular Tumoral , Depressão/genética , Depressão/psicologia , Expressão Gênica , Metiltransferases/genética , RNA Mensageiro , Regulação para CimaRESUMO
PURPOSE: Patients diagnosed with cancer often suffer from emotional stressors, such as anxiety, depression, and fear of death. However, whether fear stress could influence the glioma progression is still unclear. METHODS: Xenograft glioma animal models were established in nude mice. Tumor-bearing mice were subjected to fear stress by living closely with cats and then their depressive behaviors were measured using an open field test. Hematoxylin and eosin staining, the TUNEL staining and immunochemical staining were used to detect the histopathological changes of tumor tissues. Gene expression profiling was used to screen the aberrant gene expression. Methylated RNA immunoprecipitation was used to identify the RNA m6A level. Gene expression was measured by western blot and real-time PCR, respectively. RESULTS: We found that fear stress promoted glioma tumor progression in mice. Fear stress-induced upregulation of METTL3 and FSP1, increased m6A level of glioma tumor tissues, and inhibited ferroptosis in glioma progression, which were reversed by knockdown of METTL3 and FSP1 in vivo. In addition, we found that when iFSP1 (a ferroptosis inducer by targeting inhibition of FSP1) was introduced to glioma cells, the cells viability of glioma significantly was decreased and ferroptosis was enhanced in glioma cells. CONCLUSIONS: Fear stress-induced upregulation of METTL3 stabilized FSP1 mRNA by m6A modification, leading to tumor progression through inhibition of ferroptosis. Our study provides a new understanding of psychological effects on glioma development, and new insights for glioma therapy.
Assuntos
Medo , Ferroptose , Glioma , Estresse Psicológico , Animais , Humanos , Camundongos , Linhagem Celular Tumoral , Depressão/etiologia , Depressão/genética , Depressão/psicologia , Modelos Animais de Doenças , Medo/fisiologia , Medo/psicologia , Ferroptose/genética , Ferroptose/fisiologia , Expressão Gênica , Glioma/genética , Glioma/psicologia , Metiltransferases/genética , Camundongos Nus , RNA Mensageiro , Estresse Psicológico/etiologia , Estresse Psicológico/genética , Estresse Psicológico/psicologia , Regulação para Cima/genéticaRESUMO
Tumor in situ fluid (TISF) refers to the fluid at the local surgical cavity. We evaluated the feasibility of TISF-derived circulating tumor DNA (ctDNA) characterizing the genomic landscape for glioma. This retrospective study included TISF and tumor samples from 10 patients with glioma, we extracted cell-free DNA (cfDNA) from the TISF and then performed deep sequencing on that. And we compared genomic alterations between TISF and tumor tissue. Results showed that the concentration of cfDNA fragments from the patients for TISF ranged from 7.2 to 1,397 ng/ml. At least one tumor-specific mutation was identified in all 10 patients (100%). Further analysis of TISF ctDNA revealed a broad spectrum of genetic mutations, which have been reported to have clinical relevance. The analysis of concordance between TISF and tumor tissue reflected the spatiotemporal heterogeneity of glioma. Collectively, TISF ctDNA was a powerfully potential source for characterizing the genomic landscape of glioma, which provided new possibilities for precision medicine in patients with glioma.
