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Background: Neddylation, a post-translational modification process, plays a crucial role in various human neoplasms. However, its connection with kidney renal clear cell carcinoma (KIRC) remains under-researched. Methods: We validated the Gene Set Cancer Analysis Lite (GSCALite) platform against The Cancer Genome Atlas (TCGA) database, analyzing 33 cancer types and their link with 17 neddylation-related genes. This included examining copy number variations (CNVs), single nucleotide variations (SNVs), mRNA expression, cellular pathway involvement, and methylation. Using Gene Set Variation Analysis (GSVA), we categorized these genes into three clusters and examined their impact on KIRC patient prognosis, drug responses, immune infiltration, and oncogenic pathways. Afterward, our objective is to identify genes that exhibit overexpression in KIRC and are associated with an adverse prognosis. After pinpointing the specific target gene, we used the specific inhibitor MLN4924 to inhibit the neddylation pathway to conduct RNA sequencing and related in vitro experiments to verify and study the specificity and potential mechanisms related to the target. This approach is geared towards enhancing our understanding of the prognostic importance of neddylation modification in KIRC. Results: We identified significant CNV, SNV, and methylation events in neddylation-related genes across various cancers, with notably higher expression levels observed in KIRC. Cluster analysis revealed a potential trade-off in the interactions among neddylation-related genes, where both high and low levels of gene expression are linked to adverse prognoses. This association is particularly pronounced concerning lymph node involvement, T stage classification, and Fustat score. Simultaneously, our research discovered that PSMB10 exhibits overexpression in KIRC when compared to normal tissues, negatively impacting patient prognosis. Through RNA sequencing and in vitro assays, we confirmed that the inhibition of neddylation modification could play a role in the regulation of various signaling pathways, thereby influencing the prognosis of KIRC. Moreover, our results underscore PSMB10 as a viable target for therapeutic intervention in KIRC, opening up novel pathways for the development of targeted treatment strategies. Conclusion: This study underscores the regulatory function and potential mechanism of neddylation modification on the phenotype of KIRC, identifying PSMB10 as a key regulatory target with a significant role in influencing the prognosis of KIRC. [ABSTRACT FROM AUTHOR]

Background: Due to being rooted in the ground, maize (Zea mays L.) is unable to actively escape the attacks of herbivorous insects such as the Asian corn borer (Ostrinia furnacalis). In contrast to the passive damage, plants have evolved defense mechanisms to protect themselves from herbivores. Salicylic acid, a widely present endogenous hormone in plants, has been found to play an important role in inducing plant resistance to insects. In this study, we screened and identified the insect resistance gene SPI, which is simultaneously induced by SA and O. furnacalis feeding, through preliminary transcriptome data analysis. The functional validation of SPI was carried out using bioinformatics, RT-qPCR, and heterologous expression protein feeding assays. Results: Both SA and O. furnacalis treatment increased the expression abundance of SA-synthesis pathway genes and SPI in three maize strains, and the upregulation of SPI was observed strongly at 6 hours post-treatment. The expression of SPI showed a temporal relationship with SA pathway genes, indicating that SPI is a downstream defense gene regulated by SA. Protein feeding assays using two different expression vectors demonstrated that the variation in SPI protein activity among different strains is mainly due to protein modifications. Conclusions: Our research results indicate that SPI, as a downstream defense gene regulated by SA, is induced by SA and participates in maize's insect resistance. The differential expression levels of SPI gene and protein modifications among different maize strains are one of the reasons for the variation in insect resistance. This study provides new insights into ecological pest control in maize and valuable insights into plant responses to SA-induced insect resistance. [ABSTRACT FROM AUTHOR]

Exercise-induced adaptation is achieved by altering the epigenetic landscape of the entire genome leading to the expression of genes involved in various processes including regulatory, metabolic, adaptive, immune, and myogenic functions. Clinical and experimental data suggest that the methylation pattern/levels of promoter/enhancer is not linearly correlated with gene expression and proteome levels during physical activity implying a level of complexity and interplay with other regulatory modulators. It has been shown that a higher level of physical fitness is associated with a slower DNA methylation-based aging clock. There is strong evidence supporting exercise-induced ROS being a key regulatory mediator through overlapping events, both as signaling entities and through oxidative modifications to various protein mediators and DNA molecules. ROS generated by physical activity shapes epigenome both directly and indirectly, a complexity we are beginning to unravel within the epigenetic arrangement. Oxidative modification of guanine to 8-oxoguanine is a non-genotoxic alteration, does not distort DNA helix and serves as an epigenetic-like mark. The reader and eraser of oxidized guanine is the 8-oxoguanine DNA glycosylase 1, contributing to changes in gene expression. In fact, it can modulate methylation patterns of promoters/enhancers consequently leading to multiple phenotypic changes. Here, we provide evidence and discuss the potential roles of exercise-induced ROS in altering cytosine methylation patterns during muscle adaptation processes. [Display omitted] • Physical activity significantly contributes to specific DNA base methylation and oxidation signatures. • ROS modification serves not only for the re-establishment of redox homeostasis but also plays an epigenetic role. • 8-oxoGua functions as a ROS-generated epigenetic-like mark and can potentially interfere with DNA methylation. • OGG1.•8-oxoGua signaling regulates satellite cell functions, providing a new mechanism for muscle regeneration. [ABSTRACT FROM AUTHOR]