RESUMEN
Non-small-cell lung cancer (NSCLC), a common malignant tumor, requires deeper pathogenesis investigation. Autophagy is an evolutionarily conserved lysosomal degradation process that is frequently blocked during cancer progression. It is an urgent need to determine the novel autophagy-associated regulators in NSCLC. Here, we found that pirin was upregulated in NSCLC, and its expression was positively correlated with poor prognosis. Overexpression of pirin inhibited autophagy and promoted NSCLC proliferation. We then performed data-independent acquisition-based quantitative proteomics to identify the differentially expressed proteins (DEPs) in pirin-overexpression (OE) or pirin-knockdown (KD) cells. Among the pirin-regulated DEPs, ornithine decarboxylase 1 (ODC1) was downregulated in pirin-KD cells while upregulated along with pirin overexpression. ODC1 depletion reversed the pirin-induced autophagy inhibition and pro-proliferation effect in A549 and H460 cells. Immunohistochemistry showed that ODC1 was highly expressed in NSCLC cancer tissues and positively related with pirin. Notably, NSCLC patients with pirinhigh/ODC1high had a higher risk in terms of overall survival. In summary, we identified pirin and ODC1 as a novel cluster of prognostic biomarkers for NSCLC and highlighted the potential oncogenic role of the pirin/ODC1/autophagy axis in this cancer type. Targeting this pathway represents a possible therapeutic approach to treat NSCLC.
Asunto(s)
Autofagia , Carcinoma de Pulmón de Células no Pequeñas , Proliferación Celular , Progresión de la Enfermedad , Neoplasias Pulmonares , Ornitina Descarboxilasa , Femenino , Humanos , Masculino , Células A549 , Autofagia/genética , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Línea Celular Tumoral , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Ornitina Descarboxilasa/metabolismo , Ornitina Descarboxilasa/genética , Pronóstico , Regulación hacia ArribaRESUMEN
The Cd stress of Chrysanthemum indicum was treated by different concentrations of Cd Cl2 solution in the culture substrate. The content of Cd in different parts of Ch. indicum and the content of buddleoside and the total flavonoids in Ch. indicum were determined. The absorption characteristics of Cd elements in Ch. indicum were analyzed. And the influence of Cd elements on the quality of the herbs. The results showed that the application of soil Cd in the range of 0-100 mg·kg~(-1) had no significant effect on the biomass of Ch. indicum,and the root-shoot ratio showed a decreasing-increasing-decreasing trend. The content of Cd in different parts of Ch. indicum was significantly different,and the content of aboveground part was higher than that of underground part. The enrichment factors of Cd elements in different parts of Ch. indicum are different. The enrichment coefficient of aboveground parts is larger than that of underground parts. The whole parts and plants show an increase first and then decrease,and the overall enrichment factor is greater than1. The transfer coefficient of the aerial part/underground part of Ch. indicum showed a decreasing-increasing-decreasing-increasing trend with the increase of the amount of Cd applied in the soil,and the transfer coefficient was higher than 1. The contents of buddleoside and total flavonoids in Ch. indicum after Cd stress treatment were lower than the control,and the overall performance was lower and then increased,but it was still significantly lower than the control,indicating that Cd pollution directly led to the decrease of chemical quality of Ch. indicum.