Dissection of microRNA-21s role in non-small cell lung cancer

剖析 microRNA-21 在非小细胞肺癌中的作用

基本信息

批准号：
8712409
负责人：
Mark Edward Hatley
金额：
$ 16.85万
依托单位：
ST. JUDE CHILDREN'S RESEARCH HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-09-01 至 2016-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8712409
关键词：
Accounting Adenocarcinoma Cell Advisory Committees Agar Apoptosis Apoptotic BRAF gene Cancer Center Cancer Etiology Cancer Patient Cell Cycle Arrest Cell Line Cells Cessation of life Chairperson Childhood Rhabdomyosarcoma Cisplatin Clinical Collection Critiques Data Development Developmental Biology Diagnosis Disease Dissection Doctor of Philosophy Doxorubicin ERBB2 gene Early Diagnosis Environment Epidermal Growth Factor Receptor Epithelial Cells Fellowship Fostering Genes Genetic Goals Growth Human In Vitro Individual Internal Medicine KRAS2 gene Knockout Mice Laboratories Lung Lung Adenocarcinoma MEKs Malignant - descriptor Malignant Neoplasms Malignant neoplasm of lung Measures Mediating Mentors MicroRNAs Modeling Molecular Molecular Biology Molecular Profiling Mus Mutation Non-Malignant Non-Small-Cell Lung Carcinoma Normal tissue morphology Nude Mice Oncogenes Oncogenic PIK3CA gene Pathogenesis Pathway interactions Patients Pediatric Hematology/Oncology Pediatrics Pharmacology Physicians Postdoctoral Fellow Reagent Regulation Research Research Personnel Research Training Residencies Resources Role Sampling Scientist Staging Structure Testing Texas Therapeutic Intervention Time Training Training Programs Transgenic Mice Tumor Suppressor Genes Universities Work Writing Xenograft procedure advanced disease authority base cancer therapy cancer type career career development cell transformation gain of function gene discovery gene function insight loss of function lung tumorigenesis meetings member mouse model novel outcome forecast overexpression prevent professor programs research study telomere tool tumor tumor progression tumorigenesis

项目摘要

DESCRIPTION (provided by applicant): This proposal described a tailored research training program for the transition from clinical fellow to independent investigator. The principle investigator has a Ph.D. in Cell Regulation, completed a structured residency training program in Pediatrics and has just completed of clinical fellowship training in Pediatric Hematology/Oncology. The proposal described herein will foster a command on microRNA-21's (miR-21) role in the pathogenesis of non-small cell lung cancer (NSCLC). In this regard, Dr. Eric Olson the chairman of Molecular Biology at the University of Texas Southwestern and a world's authority on mouse models of microRNA and disease will serve as an ideal mentor. He has trained numerous post-doctoral fellows in the past and has sponsored previous and current physician scientists. To enhance the training, the program will enlist the expertise of Dr. John Minna, Professor of Internal Medicine and Pharmacology an expert in the molecular basis of lung cancer, Dr. Luis Parada, Chairman of Developmental Biology a premier cancer biologist and mouse geneticist, and Dr. George Lister, Chairman of Pediatrics. Furthermore, this advisory committee will not only provide regular constructive criticism of data, hypotheses, and proposed experiments but invaluable advice regarding career development as an independent and productive physician scientist. It is also expected that the members of the advisory committee will be invaluable in offering their expertise and unique reagents to foster the research plan. The research will focus on elucidating the molecular mechanisms underlying the role of miR-21 in non-small cell lung cancer. Recent work in the Olson laboratory has established that miR-21 actively participates in the pathogenesis of in a mouse model of NSCLC. MiR-21 decreases the expression of both pro-apoptotic genes and negative regulators of the Ras pathway thus facilitating tumorigenesis. The proposed experiments will build on this observation utilizing human bronchial epithelial cells and lung adenocarcinoma cell lines supported by transgenic mouse models to determine the importance of miR-21 in lung cancer and the mechanism through which miR-21 contributes to non-small cell lung cancer development. The specific aims include: 1) Determine oncogenic potential of miR-21 in immortalized human bronchial epithelial cells, 2) Define the mechanisms through which miR-21 promotes non-small cell lung cancer pathogenesis, 3) Explore miR-21 inhibition as therapy for NSCLC. The combination of the Molecular Biology Department and the NCI-Cancer Center at UT Southwestern provides an ideal setting for training physician-scientist by incorporating expertise from diverse resources into customized programs. This environment will provide the ideal interdisciplinary setting not only to conduct the proposed experiments but to develop as an independent clinician scientist from which an academic career can be constructed.

描述（由申请人提供）：该提案描述了从临床研究员到独立研究者的过渡量身定制的研究培训计划。主要调查员拥有博士学位。在细胞调节中，完成了一项小儿的结构化居住培训计划，刚刚完成了小儿血液学/肿瘤学的临床研究金培训。本文所述的提案将培养有关MicroRNA-21（miR-21）在非小细胞肺癌（NSCLC）发病机理中的作用的命令。在这方面，德克萨斯大学西南大学分子生物学主席埃里克·奥尔森（Eric Olson）博士以及世界上microRNA和疾病的老鼠模型的权威将成为理想的导师。过去，他曾经培训过许多博士后研究员，并赞助了以前和现任医师科学家。为了增强培训，该计划将获得内科和药理学教授约翰·米纳（John Minna）博士的专业知识。此外，该咨询委员会不仅将定期对数据，假设和拟议的实验进行建设性批评，而且还提供有关作为独立和生产性医师科学家职业发展的宝贵建议。还可以预期，咨询委员会的成员在提供其专业知识和独特的试剂以培养研究计划方面将是无价的。该研究将着重于阐明miR-21在非小细胞肺癌中的作用的分子机制。 Olson实验室的最新工作已经确定，MiR-21在NSCLC的小鼠模型中积极参与发病机理。 miR-21降低了RAS途径的促凋亡基因和负调节剂的表达，从而促进了肿瘤发生。提出的实验将基于通过人支气管上皮细胞和受转基因小鼠模型支持的肺腺癌细胞系和肺腺癌细胞系的基础，以确定miR-21在肺癌中的重要性以及miR-21有助于非小型细胞肺癌发育的机制。具体目的包括：1）确定miR-21在永生的人支气管上皮细胞中的致癌潜力，2）定义了miR-21促进非小细胞肺癌发病机理的机制，3）探索miR-21作为NSCLC治疗的miR-21抑制作用。 UT Southwestern的分子生物学系和NCI-CANCER中心的结合，通过将各种资源的专业知识纳入定制计划，为培训医师科学家培训医师科学家提供了理想的环境。这种环境将提供理想的跨学科环境，不仅可以进行拟议的实验，而且还可以发展为独立的临床医学家，从而可以从中建立学术职业。