Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2026 02 20 1 19 Yunfei Zhao Department of Oncology, The Fourth Clinical Medical College of Xinjiang Medical University, Urumqi, China Anna Su Department of Oncology, The Fourth Clinical Medical College of Xinjiang Medical University, Urumqi, China Rui Bai Health Management Center, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China Gulimire Adili Department of Oncology, The Fourth Clinical Medical College of Xinjiang Medical University, Urumqi, China Laxin Sabitjan Department of Oncology, The Fourth Clinical Medical College of Xinjiang Medical University, Urumqi, China Xun Li Department of Oncology, The Fourth Clinical Medical College of Xinjiang Medical University, Urumqi, China 2025 07 09 2025 09 21 This study aimed to identify a novel microRNA (miRNA)-related circulating biomarker that is easily accessible for clinical use and can dynamically monitor the biological characteristics of diffuse large B-cell lymphoma (DLBCL). We analyzed miRNA expression profiles in DLBCL from the Gene Expression Omnibus (GEO) (GSE171272 and GSE173080) and The Cancer Genome Atlas (TCGA). The immune microenvironment and immune-related gene differences associated with hsa-miR-23a-5p were assessed through the single-sample gene set enrichment analysis and CIBERSORT. Gene set enrichment analysis identified expression trends related to hsa-miR-23a-5p. The 50% inhibitory concentration of chemotherapy agents was estimated for hsa-miR-23a-5p. Potential miRNA targets were identified using TargetScan, miRWalk, and RNA22, and validated with miRTarBase, DIANA-TarBase, and NPInter. Gene functions and associated pathways were analyzed through Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes. Protein-Protein Interaction networks were built using Cytoscape. SNRPD1-related analysis was conducted using TCGA and GEO data. Hsa-miR-23a-5p was significantly overexpressed in the tumor tissues and serum exosomes of patients with DLBCL. The expression levels of hsa-miR-23a-5p were associated with distinct prognostic outcomes, immune landscapes, chemoresistance, and biological processes, serving as potential risk factors. The target gene SNRPD1 was an independent prognostic factor significantly associated with patient survival. This study identifies hsa-miR-23a-5p and its target SNRPD1 as potential prognostic factors for DLBCL. Specifically, the overexpression of hsa-miR-23a-5p in serum exosomes of patients with DLBCL suggests that it could serve as a convenient, non-invasive biomarker for clinical evaluation of DLBCL. However, further research and validation are necessary to confirm these findings. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4511 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4511/2313