Identification and Validation of an Annexin-Related Prognostic Signature and Therapeutic Targets for Bladder Cancer: Integrative Analysis

Abnormal expression and dysfunction of Annexins (ANXA1-11, 13) have been widely found in several types of cancer. However, the expression pattern and prognostic value of Annexins in bladder cancer (BC) are currently still unknown. In this study, survival analysis by our in-house OSblca web server revealed that high ANXA1/2/3/5/6 expression was significantly associated with poor overall survival (OS) in BC patients, while higher ANXA11 was associated with increased OS. Through Oncomine and GEPIA2 database analysis, we found that ANXA2/3/4/13 were up-regulated, whereas ANXA1/5/6 were down-regulated in BC compared with normal bladder tissues. Further LASSO analysis built an Annexin-Related Prognostic Signature (ARPS, including four members ANXA1/5/6/10) in the TCGA BC cohort and validated it in three independent GEO BC cohorts (GSE31684, GSE32548, GSE48075). Multivariate COX analysis demonstrated that ARPS is an independent prognostic signature for BC. Moreover, GSEA results showed that immune-related pathways, such as epithelial–mesenchymal transition and IL6/JAK/STAT3 signaling were enriched in the high ARPS risk groups, while the low ARPS risk group mainly regulated metabolism-related processes, such as adipogenesis and bile acid metabolism. In conclusion, our study comprehensively analyzed the mRNA expression and prognosis of Annexin family members in BC, constructed an Annexin-related prognostic signature using LASSO and COX regression, and validated it in four independent BC cohorts, which might help to improve clinical outcomes of BC patients, offer insights into the underlying molecular mechanisms of BC development and suggest potential therapeutic targets for BC

TaUAM3, a UDP‐Ara mutases protein, positively regulates wheat resistance to the stripe rust fungus

Abstract Plant cell walls are composed of polysaccharides such as cellulose, hemicelluloses, and pectins, whose location and function differ depending on plant type. UDP‐Ara mutases (UAMs) have been reported to play important roles in plant development and response to various plant stresses (abiotic and biotic). However, little work has been reported on UAM in wheat. In this study, we dissected the role of the UAM family member, UAM3, during the interaction between wheat and the stripe rust fungus, Puccinia striiformis f. sp. tritici (Pst), and in response to treatment with salicylic acid (SA). RNA interference (RNAi)‐based stable silencing of TaUAM3 resulted in decreased resistance to Pst fungus. In addition, CRISPR‐mediated genome editing (GE) of TaUAM3 enhanced the susceptibility of wheat to Pst or compromised disease resistance accompanied by increased fungal growth and decreased H2O2 production in plant tissues. Moreover, the transcript levels of pathogenesis‐related (PR) genes and reactive oxygen species (ROS)‐generating genes were down‐regulated in both the RNAi‐silenced and CRISPR‐edited plants, while the ROS‐scavenging gene, TaCAT3, was up‐regulated. Therefore, TaUAM3 positively regulates the resistance of wheat to Pst