RESUMEN
BACKGROUND: Lung cancer is the most prevalent cancer worldwide, with non-small cell lung cancer (NSCLC) accounting for 85% of all cases. Circular RNAs(circRNA) play crucial roles in regulating the progression of lung cancer. Despite the identification of a large number of circRNAs, their expression patterns, functions, and mechanisms of action in NSCLC development remain unclear.This study aims to investigate the transcriptional expressions, functions, and potential mechanisms of circRNA hsa_circ_0050386 in NSCLC. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was utilized for the analysis of hsa_circ_0050386 expression. Cell proliferation was detected using the IncuCyte Live Cell Analysis System and clone formation assays. Migration and invasion of NSCLC cells were evaluated through Transwell assays. Flow cytometry was performed to assay cell cycle and apoptosis. Western blot was used to investigate protein expression. Protein binding analysis was conducted by employing pull-down assays, RNA immunoprecipitation (RIP), and mass spectrometry. The role of hsa_circ_0050386 in vivo was evaluated through the use of a xenograft model. RESULTS: The study discovered that hsa_circ_0050386 displayed lower expression levels in NSCLC tissues when compared to adjacent normal tissues. Patients exhibiting lower levels of hsa_circ_0050386 expression exhibited an inverse correlation with the Clinical Stage, T-stage, and M-stage of NSCLC. Functionally, hsa_circ_0050386 suppressed the proliferation and invasion of NSCLC cells both in vitro and in vivo. A comprehensive examination exposed the interaction between hsa_circ_0050386 and RNA binding protein Serine and arginine-rich splicing factor 3 (SRSF3), resulting in the down-regulation of Fibronectin 1 (FN1) expression, which inhibits the progression of NSCLC. CONCLUSIONS: Our study shows that hsa_circ_0050386 suppresses the malignant biological behavior of NSCLC cells by down-regulating the expression of FN1, and may serve as a potential biomarker and therapeutic target for NSCLC treatment.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , MicroARNs , Humanos , Carcinoma de Pulmón de Células no Pequeñas/genética , Línea Celular Tumoral , Proliferación Celular/genética , Fibronectinas , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares/genética , ARN/genética , ARN Circular/genética , Factores de Empalme Serina-ArgininaRESUMEN
The brain metabolic changes caused by the interruption of blood supply are the initial factors of brain injury in ischemic stroke. Electroacupuncture (EA) pretreatment has been shown to protect against ischemic stroke, but whether its neuroprotective mechanism involves metabolic regulation remains unclear. Based on our finding that EA pretreatment significantly alleviated ischemic brain injury in mice by reducing neuronal injury and death, we performed a gas chromatography-time of flight mass spectrometry (GC-TOF/MS) to investigate the metabolic changes in the ischemic brain and whether EA pretreatment influenced these changes. First, we found that some glycolytic metabolites in the normal brain tissues were reduced by EA pretreatment, which may lay the foundation of neuroprotection for EA pretreatment against ischemic stroke. Then, 6[Formula: see text]h of cerebral ischemia-induced brain metabolic changes, especially the enhanced glycolysis, were partially reversed by EA pretreatment, which was manifested by the brain levels of 11 of 35 up-regulated metabolites and 18 of 27 down-regulated metabolites caused by cerebral ischemia significantly decreasing and increasing, respectively, due to EA pretreatment. A further pathway analysis showed that these 11 and 18 markedly changed metabolites were mainly involved in starch and sucrose metabolism, purine metabolism, aspartate metabolism, and the citric acid cycle. Additionally, we found that EA pretreatment raised the levels of neuroprotective metabolites in both normal and ischemic brain tissues. In conclusion, our study revealed that EA pretreatment may attenuate the ischemic brain injury by inhibiting glycolysis and increasing the levels of some neuroprotective metabolites.
Asunto(s)
Lesiones Encefálicas , Isquemia Encefálica , Electroacupuntura , Accidente Cerebrovascular Isquémico , Daño por Reperfusión , Accidente Cerebrovascular , Ratones , Animales , Electroacupuntura/métodos , Neuroprotección , Isquemia Encefálica/metabolismo , Metabolómica , Daño por Reperfusión/prevención & control , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/prevención & controlRESUMEN
Precipitation whiplash, including abrupt shifts between wet and dry extremes, can cause large adverse impacts on human and natural systems. Here we quantify observed and projected changes in characteristics of sub-seasonal precipitation whiplash and investigate the role of individual anthropogenic influences on these changes. Results show that the occurrence frequency of global precipitation whiplash is projected to be 2.56 ± 0.16 times higher than in 1979-2019 by the end of the 21st Century, with increasingly rapid and intense transitions between two extremes. The most dramatic increases of whiplash show in the polar and monsoon regions. Changes in precipitation whiplash show a much higher percentage change than precipitation totals. In historical simulations, anthropogenic greenhouse gas (GHG) and aerosol emissions have increased and decreased precipitation whiplash occurrences, respectively. By 2079, anthropogenic GHGs are projected to increase 55 ± 4% of the occurrences risk of precipitation whiplash, which is driven by shifts in circulation patterns conducive to precipitation extremes.