Nuclear protein NOP2 serves as a poor-prognosis predictor of LUAD and aggravates the malignancy of lung adenocarcinoma cells.

Recent studies have shown that NOP2, a nucleolar protein, is up-regulated in various cancers, suggesting a potential link to tumor aggressiveness and unfavorable outcomes. This study examines NOP2's role in lung adenocarcinoma (LUAD), a context where its implications remain unclear. Utilizing bioinformatics, we assessed 513 LUAD and 59 normal tissue samples from The Cancer Genome Atlas (TCGA) to explore NOP2's diagnostic and prognostic significance in LUAD. Additionally, in vitro experiments compared NOP2 expression between Beas-2b and A549 cells. Advanced databases and analytical tools, including LINKEDOMICS, STRING, and TISIDB, were employed to further elucidate NOP2's association with LUAD. Our findings indicate a significantly higher expression of NOP2 mRNA and protein in A549 cells compared to Beas-2b cells (P < 0.001). In LUAD, elevated NOP2 levels were linked to decreased Overall Survival (OS) and advanced clinical stages. Univariate Cox analysis revealed that high NOP2 expression correlated with poorer OS in LUAD (P < 0.01), a finding independently supported by multivariate Cox analysis (P < 0.05). The relationship between NOP2 expression and LUAD risk was presented via a Nomogram. Additionally, Gene Set Enrichment Analysis (GSEA) identified seven NOP2-related signaling pathways. A focal point of our research was the interplay between NOP2 and tumor-immune interactions. Notably, a negative correlation was observed between NOP2 expression and the immune infiltration levels of macrophages, neutrophils, mast cells, Natural Killer (NK) cells, and CD8 + T cells in LUAD. Moreover, the expression of NOP2 was related to the sensitivity of various chemotherapeutic drugs. In vitro, we found that downregulating NOP2 can decrease the proliferation, migration and invasion of A549 cells. Furthermore, NOP2 can regulate Caspase3-mediated apoptosis. Collectively, particularly regarding prognosis, immune infiltration and vitro experiments, these findings suggest NOP2's potential of serving as a poor-prognostic biomarker for LUAD and aggravating the malignancy of lung adenocarcinoma cells.

Upregulation of postsynaptic cAMP/PKA/CREB signaling alleviates copper(â ¡)-induced oxidative stress and pyroptosis in MN9D cells.

It has been widely reported that long-term exposure to copper increases the prevalence and mortality of Parkinson's disease. Our previous study showed that CuSO4 exposure induced a significant increase in the expression of cleaved Caspase1 proteins and the loss of dopaminergic neurons in the SNpc of mice. In this study, the effects of copper(Ⅱ) on cAMP/PKA/CREB pathway and pyroptosis-related proteins in MN9D cells were investigated by setting up copper(Ⅱ) exposure groups with different concentration gradients, to provide possible molecular evidence for studying the mechanism of copper(Ⅱ)-induced degeneration of dopaminergic neurons. We found that after 48 h of copper(Ⅱ) exposure, the cu content in MN9D cells increased in a dose-dependent manner, and the proliferation activity decreased significantly. In addition, copper(Ⅱ) exposure caused up-regulation of PDE4D and down-regulation of D1R, cAMP, PKA and p-CREB/CREB. Simultaneously, we proved that copper(Ⅱ) exposure induced oxidative stress in MN9D cells, including decreased GSH-Px content, Keap1 expression and mitochondrial membrane potential, increased malondialdehyde content, ROS intensity, and Nrf2, NQO1, HO-1, HSP-70 expression, further causing up-regulation of inflammasome and GSDMD protein. After pretreatment with Roflupram, the level of copper(Ⅱ)-induced oxidative damage decreased, the expression of inflammasome and GSDMD proteins were down-regulated. However, the protective effects of ROF were blocked by H-89. In summary, copper(Ⅱ) treatment induced oxidative stress and inflammasome-mediated pyroptosis in MN9D cells, which may be related to copper(Ⅱ)-induced postsynaptic cAMP, PKA, and CREB signal transduction disorders.