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Identification of lncRNA PRNCR1/miR-642a-5p/SSTR3 ceRNA network as novel biomarkers in detection of type 2 diabetes mellitus

ABSTRACT: Microarray analysis and RNA sequencing were performed in strictly grouped sample of peripheral blood mononuclear cells (PBMCs) from T2DM cases and healthy controls. In total, 328 upregulated and 203 downregulated lncRNAs companied with 173 upregulated and 155 downregulated mRNAs, and 24 upregulated and 18 downregulated miRNAs were identified in T2DM under a fold change filter of > 1.5 and P value < 0.05. Functional enrichment (KEGG and GO) analysis showed that differentially expressed mRNAs were mainly related to biological processes, such as cell response to endogenous stimulus, intracellular signal transduction, cGMP-PKG signaling pathway, and pancreatic secretion. Signiﬁcant downregulation of lncRNA PRNCR1, IRAIN, together with miR-1268b and SSTR3, and upregulation of lncRNA AC021491.4, miR-30c-2-3p, miR-642a-5p and TNFRSF10B were validated by quantitative real-time PCR (qRT-PCR) in T2DM compared with matched controls. PRNCR1 was localized in the cytoplasm, and AGO2 RIP and dual luciferase reporter assays indicated that PRNCR1 directly sponges miR-642a-5p to downregulate the expression of SSTR3. The receiver operating characteristic (ROC) curves showed that PRNCR1 had a high diagnostic accuracy for differentiating T2DM from healthy controls.

ORGANISM(S): Homo sapiens

PROVIDER: GSE281291 | GEO | 2025/11/18

REPOSITORIES: GEO

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Project description:MicroRNAs (miRNAs), small non-coding RNAs, are powerful and extremely versatile regulators of the gene expression in cells, playing an important role in every step of cancer progression. Here, we report a list of transcripts regulated by miR-662 and miR-24-2-5p transient overexpressions using miRNA MIMIC transfection (MIMIC-miR-662 and MIMIC-miR-24-2-5p, respectively) compared to control (MIMIC-negCTRL-FAM+) at 36 hours post-transfection in human MDA-MB-231-luc2-NW1 (NW1) (for miR-662 and miR-24-2-5p) and MCF7 (only for miR-24-2-5p) breast cancer cell lines. We found 38 transcripts significantly deregulated (17 downregulated, 21 upregulated) in miR-662-overexpressing NW1 cells compared to mock-transfected cells; 222 (187 downregulated, 35 upregulated) and 34 (32 downregulated, 2 upregulated) transcripts deregulated in miR-24-2-5p-overexpressing NW1 and MCF7 cells, respectively, compared to mock-transfected cells. Furthermore, a total of 30 transcripts (29 downregulated, 1 upregulated) were shared between miR-24-2-5p-overexpressing NW1 and MCF7 cells compared to mock-transfected cells. For miR-662, which we found to promote breast cancer metastasis by stimulating cancer cell stemness (Puppo et al., 2023), we observed the deregulation of Cell Migration Inducing Hyaluronidase 1 (CEMIP), Interleukin 6 receptor (IL6R), High Mobility Group AT-Hook 2 (HMGA2), Small Ubiquitin Like Modifier 3 (SUMO3), and Polymerase (DNA) Delta Interacting Protein 2 (POLDIP2), which reinforced the evidence of the involvement of miR-662 in the acquisition of a stem-like phenotype by human NW1 breast cancer cells and miR-662 contribution to breast cancer bone metastasis formation. For miR-24-2-5p, we found that the downregulation of two transcripts, WD Repeat and FYVE Domain Containing 1(WDFY1) and SH3 Domain Binding Glutamate Rich Protein Like 2 (SH3BGRL2), might explain a possible role of miR-24-2-5p as a tumour suppressor by reducing breast cancer cell invasive properties.

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Identification of lncRNA PRNCR1/miR-642a-5p/SSTR3 ceRNA network as novel biomarkers in detection of type 2 diabetes mellitus

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