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

项目总结： 肺癌在美国仍然是一个重要的健康负担。因此，对肺癌的功能性理解 NSCLC癌变过程中的关键分子将增强我们对其恶变的认识，并且 允许新的治疗策略。 我们最近发现了蛋白质功能效应物SncRNAs(PfeRNAs)在肿瘤发生中的关键作用。 和非小细胞肺癌的分化，描述了它们在非小细胞肺癌基础生物学中的作用，并有 阐明了它们的结构和功能特征。我们已经确定了8个pfeRNA是有希望的非侵入性的 应用SncRNAs深度测序技术分析108例生物样本的生物标志物，包括(I)健康人血浆 对照，(Ii)来自I/II期NSCLC患者的血浆和匹配的活检证实的NSCLC组织以及 组织学正常的邻近肺组织，和(Iii)来自经活检证实的良性和非典型肺炎患者的血浆。 恶性肺结节。我们已经在352个临床生物样本中验证了这些生物标志物，包括 正常对照组77例，良性病变44例，恶性肺结节231例。这些 8个pfeRNAs能够：(1)区分有无肺结节的患者，具有敏感性 特异性分别高达98.1%和100%；(2)鉴别恶性与非恶性 肺良性结节的敏感性和特异性分别为78%和78.8%。此外， 我们鉴定了一个pfeRNA是ADC特异的，两个pfeRNA是SCC特异的。另外，我们已经确认 对这三个pfeRNAs逐一进行功能分析，确定了它们在初级生物中的作用 ADC、SCC和HBE细胞的体外活性。此外，我们指定了这三个细胞的分布 荧光原位杂交(FISH)检测pFeRNAs。数据有力地表明，这三个人 PfeRNAs在非小细胞肺癌的发生、发展中起重要作用。因此，在这个项目中，我们将 确定这三个pfeRNAs的目标蛋白，并研究其相互作用的机制 与目标蛋白的结合。该项目将为非小细胞肺癌的致癌机制提供新的证据。

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.