RESUMO
BACKGROUND: Several proteins in the tripartite-motif (TRIM) family are associated with the development of colorectal cancer (CRC), but research on the role of TRIM69 was lacking. The present study examined the correlation between TRIM69 expression and colon adenocarcinoma (COAD). METHODS: mRNA sequencing data for COAD patients was extracted from The Cancer Genome Atlas to analyze correlations between TRIM69 expression and patients' clinical features as well as survival. Potential associations with immune cells and chemosensitivity also were predicted using various algorithms in the TIMER, Limma, clusterProfiler, GeneMANIA, and Gene Set Cancer Analysis platforms. Subsequently, polymerase chain reaction analysis and immunohistochemical staining were used to detect TRIM69 expression in COAD tissue samples from real-world patients. RESULTS: TRIM69 expression was lower in COAD tissues than in normal tissues and correlated with the pathologic stage and metastasis (M category). Additionally, TRIM69 was found to be involved in several immune-related pathways, notably the NOD-like signaling pathway. These results suggest that high TRIM69 expression has the potential to enhance tumor sensitivity to 5-fluorouracil and programmed cell death protein 1 (PD-1) blockers. CONCLUSIONS: From our findings that TRIM69 expression was significantly reduced in COAD compared with non-cancer tissues and associated with pathologic stage and metastasis, we conclude that increasing TRIM69 expression and/or activity may help to improve therapeutic outcomes. Accordingly, TRIM69 represents a potentially valuable marker of metastasis and target for adjuvant therapy in COAD.
Assuntos
Adenocarcinoma , Neoplasias do Colo , Humanos , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/genética , Fluoruracila/uso terapêutico , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Receptor de Morte Celular Programada 1 , Algoritmos , Proteínas com Motivo Tripartido/genética , Ubiquitina-Proteína Ligases/genéticaRESUMO
Streptococcus aglactiae(GBS) infection in tilapia is a serious global disease that causes significant production loss. Here, we studied the role of GBS in the spleen and the spleen's response against the pathogen through dual RNA-seq and proteome technology. Animals were divided into three groups: control, virulent treated (HN016), and attenuated treated (YM001). Spleen samples were collected and analysis when a disease outbreak. Dual RNA-seq result showed the virulence factor genes of GBS, included CAMP factor, PGK, OCT, enolase, scpB, Sip, bca, were upregulation. downregulation of GapA, cylE, OCT, scpB, C5AP, rlmB, hly, FBP, in HN016 and YM001. But for proteomic, OCT and bca were downregulation, the others were upregulation. For host transcriptome KEGG analysis showed, the NOD-like receptor signaling pathway (NLRs) and TOLL-like receptor signaling pathway (TLRs) were upreguoation in HN016 infected fish than the control fish; But for proteome KEGG, only the NLRS was up, the TLRS was not change. Compared with YM001 infected fishes, for transcriptome, NLRs and TLRs in infected HN016 fishes were significance rise (pâ¯<â¯0.01); for proteome, the NLRs was up (pâ¯<â¯0.05), but TLRs was no change.Analysis of pathogen-host interaction showed that the peptidoglycan (PNG), CD2, LCK, and host's Zap70 were involved in the regulation of NLRs; PNG, LCK, and ZAP70 were involved in the regulation of TRLs. Conclusion: the virulent strain HN016 and attenuated strainYM001 differed in the quantity of virulence factors. In tilapia's innate immune system, NLRs was the main defense factors, but bacteria avoided the host defense through TLRs.
Assuntos
Ciclídeos , Doenças dos Peixes/imunologia , Proteínas de Peixes/genética , Proteínas Adaptadoras de Sinalização NOD/genética , Baço/imunologia , Infecções Estreptocócicas/veterinária , Streptococcus agalactiae/fisiologia , Animais , Doenças dos Peixes/genética , Doenças dos Peixes/microbiologia , Proteínas de Peixes/metabolismo , Perfilação da Expressão Gênica/veterinária , Proteínas Adaptadoras de Sinalização NOD/metabolismo , Proteoma , Proteômica , RNA-Seq/veterinária , Infecções Estreptocócicas/genética , Infecções Estreptocócicas/imunologia , Infecções Estreptocócicas/microbiologia , TranscriptomaRESUMO
Systemic lupus erythematosus (SLE) is a persistent autoimmune disorder that can culminate in lupus nephritis (LN), an intricate renal complication. In pursuit of unraveling the intricate molecular underpinnings governing LN progression, we conducted bioinformatics analysis employing gene expression data sourced from the GSE32591 dataset. Our scrutiny revealed a panoply of differentially expressed genes (DEGs) within the glomerulus and tubulointerstitial compartments of LN patients. Enrichment analysis for DEGs engaged in diverse processes, encompassing virus defense, viral life cycle, cell adhesion molecules, and the NOD-like receptor signaling pathway. Notably, STAT1 emerged as an eminent central hub gene intrinsically tied to NOD-like receptor signaling. To explore the functional significance of STAT1 in the context of LN, MRL-lpr mice model was used to knockout STAT1. The results unveiled that STAT1 silencing yielded a migratory effect on kidney injury, concurrently curbing inflammatory markers. Meanwhile, knockout STAT1 also reduced NLRP3 expression and Cleaved caspase-1 expression. These findings offer tantalizing prospects for targeting STAT1 as a potential therapeutic conduit in the management of LN.