非编码RNA（TP53TG1、LINC00342、MALAT1、DNM3OS、miR-126-3p、miR-200a-3p、miR-18a-5p）与蛋白质编码基因（PTEN、FOXO3）的差异表达与特发性肺纤维化风险的关系
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.
作者信息
Korytina Gulnaz F, Markelov Vitaly A, Gibadullin Irshat A, Zulkarneev Shamil R, Nasibullin Timur R, Zulkarneev Rustem H, Avzaletdinov Arthur M, Avdeev Sergey N, Zagidullin Naufal Sh
机构信息
Institute of Biochemistry and Genetics-Subdivision of the Ufa Federal Research Centre of the Russian Academy of Sciences (IBG UFRC RAS), Pr. Oktyabrya, 71, Ufa, 450054, Russian Federation.
Bashkir State Medical University, Lenina Str. 3, Ufa, 450008, Russian Federation.
出版信息
Biochem Genet. 2025 Jan 29. doi: 10.1007/s10528-024-11012-z.
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). 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.
特发性肺纤维化（IPF）是一种发病机制不明的快速进展性间质性肺疾病，目前尚无有效治疗方法。鉴于长链非编码RNA（TP53TG1、LINC00342、H19、MALAT1、DNM3OS、MEG3）、微小RNA（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）在转化生长因子-β/信号转导分子3（TGF-β/SMAD3）、Wnt/β-连环蛋白、黏着斑和磷脂酰肌醇-3激酶/蛋白激酶B（PI3K/AKT）信号通路中的调控作用，我们研究了IPF患者外周血单个核细胞（PBMC）和肺组织中所选基因的表达水平。收集了33例新诊断的、未接受过治疗的患者及70例健康对照者的肺组织和血液样本。采用逆转录定量聚合酶链反应（RT-qPCR）分析基因表达水平。运用TaqMan分析和TaqMan微小RNA分析对靶长链非编码RNA、信使核糖核酸（mRNA）和微小RNA的表达进行定量。我们的研究发现，与健康对照相比，IPF患者PBMC中存在显著差异表达的基因，包括长链非编码RNA MALAT1（倍数变化=3.809，P=0.0001）、TP53TG1（倍数变化=0.4261，P=0.0021）和LINC00342（倍数变化=1.837，P=0.0448）；微小RNA miR-126-3p（倍数变化=0.102，P=0.0028）、miR-200a-3p（倍数变化=0.442，P=0.0055）和miR-18a-5p（倍数变化=0.154，P=0.0034）；以及mRNA FOXO3（倍数变化=4.604，P=0.0032）和PTEN（倍数变化=2.22，P=0.0011）。在IPF患者的肺组织中，观察到TP53TG1（倍数变化=0.2091，P=0.0305）和DNM3OS（倍数变化=4.759，P=0.05）有显著表达变化。对TP53TG1、MALAT1、微小RNA miR-126-3p和PTEN的PBMC表达水平进行联合分析，区分IPF患者和健康对照的曲线下面积（AUC）=0.971，灵敏度=0.80，特异性=0.955（P= 6×10）。这些发现表明，所鉴定的非编码RNA和mRNA可能参与了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长链非编码RNA、微小RNA及其靶标促成肺纤维化（PF）的精确分子机制。
Zotero 插件