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MicroRNA and Transcription Factor Co-regulation in Cancer

癌症中的 MicroRNA 和转录因子共同调控

基本信息

批准号：
9329385
负责人：
Zhongming Zhao
金额：
$ 20.1万
依托单位：
UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-08-09 至 2019-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9329385
关键词：
Biological Cancer Prognosis Clinical Colon Carcinoma Colorectal Cancer Complex Data Data Set Development Diagnosis Disease Ethnic Origin Foundations Freezing Gender Gene Expression Profile Gene Expression Regulation Genes Genetic Transcription Genomics Glioblastoma Heterogeneity Investigation Knowledge Literature Malignant Neoplasms Malignant neoplasm of lung Malignant neoplasm of ovary Mediating Messenger RNA Meta-Analysis MicroRNAs Modeling Molecular Profiling National Human Genome Research Institute Normal tissue morphology Oncogenes Output Pathogenesis Pathway Analysis Patients Pilot Projects Prevention Procedures Property Publishing Regulation Regulator Genes Reporting Role Sampling Seeds Statistical Methods System The Cancer Genome Atlas Therapeutic Time Tissues Tumor Suppressor Proteins Validation cancer biomarkers cancer cell cancer diagnosis cancer subtypes cancer type cell type cohort computer framework established cell line evidence base experimental study genome-wide innovation insight novel outcome forecast public health relevance success therapeutic target tool transcription factor transcriptome transcriptomics treatment response treatment strategy tumor tumorigenesis

项目摘要

DESCRIPTION (provided by applicant): Recent studies have implicated the critical roles of microRNAs (miRNAs) in the pathogenesis of cancer, suggesting that miRNAs can be clinically useful as biomarkers for cancer prognosis, diagnosis and treatment. To date, the miRNA information in cancer studies has varied greatly due to data heterogeneity and disease complexity. In this application, in Aim 1, we will develop novel statistical methods to systematically perform meta- analysis of miRNA expression in the first four cancers (glioblastoma, ovarian cancer, colorectal cancer, and lung cancer) reported by The Cancer Genome Atlas (TCGA) project. For each of these cancers, more than 300 dysregulated miRNAs have been reported, which makes this aim not only feasible but immediately needed. In Aim 2, we will develop innovative strategies to explore miRNAs' functions in cancer through miRNA and transcription factor (TF) co-regulatory network analysis. For each cancer, we will build cancer-specific regulatory networks using miRNA/mRNA co-expression profiling and TF/gene regulation derived from the corresponding TCGA dataset. We will then identify network modules that reflect miRNA and TF co-regulation in cancer. We will investigate both common regulatory modules among four types of cancer and unique modules for each specific cancer. In Aim 3, we will experimentally validate selected miRNAs and their targets in common regulatory modules from Aim 2 using already available tissue and matched normal samples as well as established cell lines. This application will be the first systematic investigation of all available miRNA studes in the first four TCGA cancers. The successful completion of Aim 1 will provide us with a list of evidence-based miRNAs in glioblastoma, ovarian cancer, colorectal cancer, and lung cancer; the successful completion of Aim 2 will provide us with a comprehensive exploration of miRNA and TF co-regulation at the regulatory network level in these cancers; the successful completion of Aim 3 will validate our meta- and network- approaches, help us understand the miRNA regulatory mechanisms, and provide us with potential therapeutic targets in these cancers. Although quite exploratory, we expect this project is highly feasible and timely due to the large amount of data available in literature and from TCGA. This pioneering effort to detect functionally important miRNAs in complex diseases will greatly enhance our understanding of the regulatory systems in cancer, which will likely lead to the development of effective prevention, diagnosis, and treatment strategies.