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Identification of the LncRNA PRNCR1/miR-642a-5p/SSTR3 CeRNA network and its diagnostic value in type 2 diabetes mellitus
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DOI：10.1186/s13098-025-02061-4.png)
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Abstract
En 中文
This study aimed to investigate the expression and functions of long noncoding RNAs (lncRNAs) in circulating leukocytes related to type 2 diabetes mellitus (T2DM). We conducted microarray analysis and RNA sequencing on peripheral blood mononuclear cells (PBMCs) from newly diagnosed T2DM patients and healthy controls. Differentially expressed lncRNAs, mRNAs, and miRNAs were identified using an absolute log2(Fold Change) of ≥ 0.585 cutoff and a P value < 0.05. A competing endogenous RNA (ceRNA) network was constructed, and functional enrichment analyses (Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO)) were performed. Quantitative real-time PCR (qRT-PCR) was used to validate the expression of selected lncRNAs, miRNAs, and mRNAs. Correlations with clinical parameters were assessed, and receiver operating characteristic (ROC) curve analysis was performed to evaluate their potential as biomarkers. Dual-luciferase and RNA immunoprecipitation (RIP) assays were used to validate the interactions within the ceRNA network. A total of 531 DElncRNAs, 328 DEmRNAs, and 42 DEmiRNAs were identified in PBMCs from T2DM patients compared to healthy controls. The ceRNA network included 24 differentially expressed lncRNAs, 11 miRNAs, and 18 mRNAs. Functional enrichment analyses indicated that the differentially expressed mRNAs were mainly associated with pancreatic secretion, lipid metabolism, atherosclerosis, type I diabetes mellitus, and fluid shear stress. Furthermore, qRT-PCR validation confirmed the significant downregulation of prostate pancer associated non-coding RNA 1 (PRNCR1) and somatostatin receptor 3 (SSTR3), and the upregulation of miR-642a-5p. PRNCR1 and miR-642a-5p were positively correlated with triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), HbA1c, fasting plasma glucose (FPG), and homeostasis model assessment of insulin resistance (HOMA-IR), while negatively correlated with leptin and insulin. Conversely, SSTR3 was positively correlated with leptin and insulin, while negatively correlated with total cholesterol (TC), TG, LDL-C, HbA1c, FPG, and HOMA-IR. ROC curve analysis suggested that the expression of miR-642a-5p and SSTR3 could differentiate T2DM patients from healthy controls. Dual-luciferase and RIP assays confirmed that PRNCR1 could sponge miR-642a-5p, which in turn regulated SSTR3, and PRNCR1 knockdown was demonstrated to significantly downregulate SSTR3. These findings suggest that PRNCR1 may contribute to insulin secretion disorders in T2DM by regulating the miR-642a-5p/SSTR3 axis, and gained new insight into the potential mechanisms and pathways involved in T2DM.
Keywords:
LncRNA PRNCR1
MiR-642a-5p
SSTR3
Type 2 diabetes mellitus
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