High expression of RNF169 is associated with poor prognosis in pancreatic adenocarcinoma by regulating tumour immune infiltration

Abstract

Background: Pancreatic adenocarcinoma (PAAD) is a highly deadly and aggressive tumour with a poor prognosis. However, the prognostic value of RNF169 and its related mechanisms in PAAD have not been elucidated. In this study, we aimed to explore prognosis-related genes, especially RNF169 in PAAD and to identify novel potential prognostic predictors of PAAD.Methods: The GEPIA and UALCAN databases were used to investigate the expression and prognostic value of RNF169 in PAAD. The correlation between RNF169 expression and immune infiltration was determined by using TIMER and TISIDB. Correlation analysis with starBase was performed to identify a potential regulatory axis of lncRNA-miRNA-RNF169.Results: The data showed that the level of RNF169 mRNA expression in PAAD tissues was higher than that in normal tissues. High RNF169 expression was correlated with poor prognosis in PAAD. In addition, analysis with the TISIDB and TIMER databases revealed that RNF169 expression was positively correlated with tumour immune infiltration in PAAD. Correlation analysis suggested that the long non-coding RNA (lncRNA) AL049555.1 and the microRNA (miRNA) hsa-miR-324-5p were involved in the expression of RNF169, composing a potential regulatory axis to control the progression of PAAD. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated that RNF169 plays a role in PAAD through pathways such as TNF, Hippo, JAK-STAT and Toll-like receptor signaling.Conclusion: In summary, the upregulation of RNF169 expression mediated by ncRNAs might influence immune cell infiltration in the microenvironment; thus, it can be used as a prognostic biomarker and a potential therapeutic target in PAAD.

Insights from the protein interaction Universe of the multifunctional “Goldilocks” kinase DYRK1A

“…RNF169 is a 77 kDa protein that contains an N-terminal RING finger motif, a central MIU1 and a C-terminal MIU2 (motif interacting with ubiquitin) domains that recognizes the ubiquitinated histone marks and accumulates near the DNA double strand break (DSB) lesions ( Chen et al, 2012 ; Panier et al, 2012 ; Poulsen et al, 2012 ). The role of RNF169 in development and human disease has not been extensively investigated; it was suggested that that high expression of RNF169 could be a prognostic marker in pancreatic ductal carcinoma although this association has not been experimentally validated yet ( Wang J. et al, 2022 ). Due to its lack of enzymatic activity, RNF169 antagonizes the function of its close homologue RNF168 an active ubiquitin ligase that recognizes the same K13/K15-ubiquitinated H2A and amplifies the DNA damage response by further ubiquitinating its substrates at site of the lesion ( Hu et al, 2017 ; Kitevski-LeBlanc et al, 2017 ; An et al, 2018 ).…”