Identify the target proteins of one ADC-specific and two SCC-specific pfeRNAs and investigate the mechanisms underlying the pfeRNA-protein interaction.

鉴定一种 ADC 特异性 pfeRNA 和两种 SCC 特异性 pfeRNA 的靶蛋白，并研究 pfeRNA-蛋白质相互作用的机制。

• 批准号: 10579497
• 负责人: Yuping Mei
• 金额: $ 8.19万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-03-01 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10579497
• 关键词: Adenocarcinoma; Antibodies; Automobile Driving; Benign; Binding; Biological; Biological Assay; Biological Markers; Biology; Biopsy; Biotin; Cancer Etiology; Cells; Cessation of life; Characteristics; Clinical; Clinical Data; Computer software; Cytoplasm; Data; Data Set; Development; Diagnosis; Disease; Ectopic Expression; Elements; Fluorescence Resonance Energy Transfer; Fluorescent in Situ Hybridization; Fractionation; Health; Histologic; Human; Immunoprecipitation; Immunotherapy; In Vitro; Knowledge; Label; Liquid Chromatography; Lung; Lung nodule; Malignant - descriptor; Malignant Neoplasms; Malignant neoplasm of lung; Measures; Molecular; Mutation; Non-Small-Cell Lung Carcinoma; Nuclear; Oligonucleotides; Oncogenic; Patients; Pattern; Plasma; Play; Prognosis; Protein Inhibition; Proteins; Publications; RNA-Binding Proteins; Research; Role; Sensitivity and Specificity; Solid; Specific qualifier value; Specificity; Squamous cell carcinoma; Structure of parenchyma of lung; Survival Rate; Tertiary Protein Structure; Testing; Tissues; United States; biomarker validation; deep sequencing; improved; knock-down; mutant; novel; novel therapeutic intervention; protein activation; protein complex; protein expression; protein function; tandem mass spectrometry; targeted treatment; tumorigenesis

Project Summary: Lung cancer continues to be a significant health burden in the U.S. Thus, a functional understanding of the critical molecules during NSCLC oncogenesis will enhance our knowledge of its malignant transformation, and allow novel therapeutic strategies. We have recently identified critical roles of protein function effector sncRNAs (pfeRNAs) in the tumorigenesis and differentiation of NSCLC, have described their functions in the basic biology of NSCLC, and have elucidated their structural and functional features. We have identified eight pfeRNAs as promising non-invasive biomarkers using sncRNAs deep sequencing by analyzing 108 biospecimens, including (i) plasma from healthy controls, (ii) plasma from patients with Stage I/II NSCLC with matched biopsy-proven NSCLC tissue as well as histologically normal adjacent lung tissue, and (iii) plasma from patients with both biopsy-proven benign and malignant lung nodules. We have already validated these biomarkers in 352 clinical biospecimens, including 77 healthy controls, 44 patients with benign disease, and 231 patients with malignant lung nodules. These eight pfeRNAs were able to: (1) to differentiate patients with or without pulmonary nodules, with a sensitivity and specificity up to 98.1% and 100%, respectively; (2) to differentiate patients who had malignant versus benign pulmonary nodules, with a sensitivity and a specificity up to 78% and 78.8%, respectively. Furthermore, we identified a pfeRNA is ADC-specific and two pfeRNAs are SCC-specific. Besides, we have confirmed functional analyses of these three pfeRNAs one by one and identified their roles in the primary biological activities of ADC, SCC, and HBE cells in vitro. In addition, we specified the cellular distribution of these three pfeRNAs by fluorescence in situ hybridization (FISH) assay. The data strongly suggest that these three pfeRNAs play critical roles in tumorigenesis and cancer development of NSCLC. Thus, in this project, we will identify the target proteins of these three pfeRNAs and investigate the mechanisms underlying the interaction with the target proteins. This project will provide new evidence on NSCLC oncogenesis.

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