Identify new pseudogene RPL7P1-oriented network as a drug target against infections pre-existing diabetes.

Abstract

Background: Diabetes coexisting with infections (DCI) significantly increases the risk of severe outcomes and mortality in patients. This study proposes that RPL7P1, an uncharacterized pseudogene, plays a role in the pathogenesis of DCI.

Methods: Using a multifaceted approach, we employed experimental datasets from ENCODE to identify key genes. Drug repositioning was performed using gene network analysis with z-scores and the ROCR package. Network expansion was facilitated by NetworkAnalyst's core algorithms, with disease validation through the NHGRI GWAS Catalog. Cytoscape was utilized for network visualization.

Results: Our findings reveal RPL7P1's potential involvement in DCI through modulation of CBL and STXBP3 by sequestering hsa-miR-144-3p, interaction with IGF2BP2 protein, and crosstalk with ATP6V1E1 RNA. Single-cell profiling pinpointed endothelial cells as a potential signaling nexus. Therapeutic agents targeting the RPL7P1-centric network showed promise in managing infections in diabetic patients. Additionally, we identified key molecular players, the m6A modification of RPL7P1, and its role in cuproptosis-a novel form of cell death.

Conclusion: This research elucidates the potential role of the novel pseudogene RPL7P1 in DCI, highlighting the importance of pseudogenes in complex diseases and providing novel insights into the epigenetic modulation of diabetes complicated by infections. Insight Box Diabetes and infections often coexist, complicating our understanding of their shared mechanisms. To address this, we employed a comprehensive suite of bioinformatics methods, including pathway mapping, ceRNA analysis, PPI evaluation, single-cell dissection, network modeling, and drug repositioning strategies. Our research revealed that RPL7P1 modulates signaling pathways by sponging miR-144-3p, interacting with IGF2BP2 and ATP6V1E1 RNA, and influencing cuproptosis-a novel form of cell death-through m6A modification, a key RNA modification. We identified endothelial cells as key mediators of the RPL7P1 network in the liver. Additionally, our integrative approach uncovered five potential therapeutic drugs targeting the RPL7P1 network. These findings provide novel insights into coexisting diabetes and infections, underscoring the value of multidisciplinary strategies in uncovering coexisting disease mechanisms and treatment opportunities.