非编码rna （TP53TG1、LINC00342、MALAT1、DNM3OS、miR-126-3p、miR-200a-3p、miR-18a-5p）和蛋白编码基因（PTEN、FOXO3）差异表达与特发性肺纤维化风险的关系

IF 2.1 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical Genetics Pub Date : 2025-01-29 DOI:10.1007/s10528-024-11012-z

Gulnaz F Korytina, Vitaly A Markelov, Irshat A Gibadullin, Shamil R Zulkarneev, Timur R Nasibullin, Rustem H Zulkarneev, Arthur M Avzaletdinov, Sergey N Avdeev, Naufal Sh Zagidullin

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引用次数: 0

摘要

特发性肺纤维化（IPF）是一种快速进展的间质性肺疾病，发病机制尚不清楚，目前尚无有效的治疗方法。考虑到lncRNAs （TP53TG1、LINC00342、H19、MALAT1、DNM3OS、MEG3）、miRNAs （miR-218-5p、miR-126-3p、miR-200a-3p、miR-18a-5p、miR-29a-3p）及其靶蛋白编码基因（PTEN、TGFB2、FOXO3、KEAP1）在TGF-β/SMAD3、Wnt/β-catenin、局灶黏附和PI3K/AKT信号通路中的调控作用，我们研究了所选基因在IPF患者外周血单核细胞（PBMCs）和肺组织中的表达水平。研究人员收集了33名新诊断、未接受治疗的患者和70名健康对照者的肺组织和血液样本。RT-qPCR分析基因表达水平。采用TaqMan法和TaqMan MicroRNA法定量靶lncrna、mrna和mirna的表达。我们的研究发现，与健康对照相比，IPF患者的PBMCs表达存在显著差异，包括lncRNAs MALAT1 （Fold Change = 3.809, P = 0.0001）、TP53TG1 （Fold Change = 0.4261, P = 0.0021）和LINC00342 (Fold Change = 1.837, P = 0.0448)；miRNAs miR-126-3p （Fold Change = 0.102, P = 0.0028）、miR-200a-3p （Fold Change = 0.442, P = 0.0055）和miR-18a-5p (Fold Change = 0.154, P = 0.0034)；mrna FOXO3 （Fold Change = 4.604, P = 0.0032）和PTEN （Fold Change = 2.22, P = 0.0011）。在IPF患者肺组织中，TP53TG1 （Fold Change = 0.2091, P = 0.0305）和DNM3OS （Fold Change = 4.759, P = 0.05）的表达发生显著变化。联合分析PBMCs中TP53TG1、MALAT1、miRNA miR-126-3p和PTEN的表达水平，将IPF患者与健康对照区分开，AUC = 0.971，敏感性= 0.80，特异性= 0.955 （P = 6 × 10-8）。这些发现表明鉴定的ncrna和mrna可能参与IPF的发病机制。然而，需要进一步的功能验证研究来阐明这些lncrna、mirna及其靶点参与PF的精确分子机制。

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The Relationship Between Differential Expression of Non-coding RNAs (TP53TG1, LINC00342, MALAT1, DNM3OS, miR-126-3p, miR-200a-3p, miR-18a-5p) and Protein-Coding Genes (PTEN, FOXO3) and Risk of Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a rapidly progressive interstitial lung disease of unknown pathogenesis with no effective treatment currently available. Given the regulatory roles of lncRNAs (TP53TG1, LINC00342, H19, MALAT1, DNM3OS, MEG3), miRNAs (miR-218-5p, miR-126-3p, miR-200a-3p, miR-18a-5p, miR-29a-3p), and their target protein-coding genes (PTEN, TGFB2, FOXO3, KEAP1) in the TGF-β/SMAD3, Wnt/β-catenin, focal adhesion, and PI3K/AKT signaling pathways, we investigated the expression levels of selected genes in peripheral blood mononuclear cells (PBMCs) and lung tissue from patients with IPF. Lung tissue and blood samples were collected from 33 newly diagnosed, treatment-naive patients and 70 healthy controls. Gene expression levels were analyzed by RT-qPCR. TaqMan assays and TaqMan MicroRNA assay were employed to quantify the expression of target lncRNAs, mRNAs, and miRNAs. Our study identified significant differential expression in PBMCs from IPF patients compared to healthy controls, including lncRNAs MALAT1 (Fold Change = 3.809, P = 0.0001), TP53TG1 (Fold Change = 0.4261, P = 0.0021), and LINC00342 (Fold Change = 1.837, P = 0.0448); miRNAs miR-126-3p (Fold Change = 0.102, P = 0.0028), miR-200a-3p (Fold Change = 0.442, P = 0.0055), and miR-18a-5p (Fold Change = 0.154, P = 0.0034); and mRNAs FOXO3 (Fold Change = 4.604, P = 0.0032) and PTEN (Fold Change = 2.22, P = 0.0011). In lung tissue from IPF patients, significant expression changes were observed in TP53TG1 (Fold Change = 0.2091, P = 0.0305) and DNM3OS (Fold Change = 4.759, P = 0.05). Combined analysis of PBMCs expression levels for TP53TG1, MALAT1, miRNA miR-126-3p, and PTEN distinguished IPF patients from healthy controls with an AUC = 0.971, sensitivity = 0.80, and specificity = 0.955 (P = 6 × 10^-8). These findings suggest a potential involvement of the identified ncRNAs and mRNAs in IPF pathogenesis. However, additional functional validation studies are needed to elucidate the precise molecular mechanisms by which these lncRNAs, miRNAs, and their targets contribute to PF.

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来源期刊

Biochemical Genetics 生物-生化与分子生物学

CiteScore

3.90

自引率

0.00%

发文量

133

审稿时长

4.8 months

期刊介绍： Biochemical Genetics welcomes original manuscripts that address and test clear scientific hypotheses, are directed to a broad scientific audience, and clearly contribute to the advancement of the field through the use of sound sampling or experimental design, reliable analytical methodologies and robust statistical analyses. Although studies focusing on particular regions and target organisms are welcome, it is not the journal’s goal to publish essentially descriptive studies that provide results with narrow applicability, or are based on very small samples or pseudoreplication. Rather, Biochemical Genetics welcomes review articles that go beyond summarizing previous publications and create added value through the systematic analysis and critique of the current state of knowledge or by conducting meta-analyses. Methodological articles are also within the scope of Biological Genetics, particularly when new laboratory techniques or computational approaches are fully described and thoroughly compared with the existing benchmark methods. Biochemical Genetics welcomes articles on the following topics: Genomics; Proteomics; Population genetics; Phylogenetics; Metagenomics; Microbial genetics; Genetics and evolution of wild and cultivated plants; Animal genetics and evolution; Human genetics and evolution; Genetic disorders; Genetic markers of diseases; Gene technology and therapy; Experimental and analytical methods; Statistical and computational methods.