长链非编码RNA在癌症中的表观遗传机制-猫眼课题宝

长链非编码RNA在癌症中的表观遗传机制

批准号：

8797489

负责人：

Lin Zhang

金额：

$36.6万

依托单位：

UNIVERSITY OF PENNSYLVANIA

依托单位国家：

美国

项目类别：

财政年份：

2015

资助国家：

美国

项目状态：

已结题

起止时间：

2015-04-06 至 2020-03-31

来源：

https://reporter.nih.gov/project-details/8797489

关键词：

B-Cell Lymphomas BMI1 gene Biochemical Biological Markers CDKN1A gene Cancer cell line Cell physiology Cells ChIP-seq Chromatin Code Complex Core Protein DNA Sequence Alteration Data Disease Epigenetic Process Epithelial Exhibits Figs - dietary Gene Expression Regulation Genes Genetic Screening Genetic Transcription Genome Guide RNA Hereditary Disease Homologous Gene Human Human Genome Informatics Investigation Laboratories Lead Libraries Malignant - descriptor Malignant Neoplasms MicroRNAs Modeling Molecular Nature Neoplasm Metastasis Oncogenic Outcome PRC1 Protein Pathology Pathway interactions Patients Process Proteins RNA RNA Binding RNA-Protein Interaction Recruitment Activity Regulation Reporting Repression Research Resources Ribonucleoproteins Role Small Interfering RNA Specimen System Technology Testing The Cancer Genome Atlas Transcript Transgenic Mice Untranslated RNA Xenograft Model base cancer cell cancer genome cancer initiation cancer type clinical application in vivo infancy mouse model new therapeutic target novel oncology public health relevance scaffold screening senescence therapeutic target transcriptome sequencing tumor tumor growth tumor initiation tumor progression

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英文摘要

DESCRIPTION (provided by applicant): Cancer is a genetic disease involving multi-step changes in the genome. The human genome contains ~25,000 protein-coding genes, representing less than 2% of the total genome, whereas up to 70% of the human genome is transcribed into RNA, yielding many thousands of non-coding RNAs. The recent discovery of non-coding RNAs, including small non-coding RNAs such as microRNA, has dramatically altered our understanding of cancer. However, research on long non-coding transcripts is still in its infancy. Long non-coding RNAs (lncRNAs) are operationally defined as RNA transcripts larger than 200 nt that do not appear to have protein-coding potential. Rapidly accumulating evidence indicates that lncRNA is involved in the initiation and progression of cancer. A novel oncogenic lncRNA, FAL1 (Focal Amplified lncRNA 1), has recently been identified by the PI's laboratory. Our preliminary data indicate that: amplification and high expression of FAL1 are correlated with poorer outcomes in cancer; FAL1 RNA associates with the epigenetic repressor BMI1, regulating its stability; knockdown of FAL1 increases the transcription of a number of genes, including CDKN1A; the oncogenicity of FAL1 is partially attributable to its repression of p21 expression; and FAL1-specific small interfering RNAs significantly inhibit tumor growth in vivo. Therefore, we hypothesize that the novel oncogenic lncRNA FAL1 epigenetically regulates multiple cancer-associated pathways via its interaction with BMI1, and that the investigation of the function of FAL1 may provide novel biomarkers and therapeutic targets for patients with cancer. We will test this hypothesis through the following specific aims: Specific Aim 1. Characterize the molecular mechanisms by which FAL1 regulates BMI1 stability. Specific Aim 2. Identify the molecular network epigenetically regulated by FAL1/BMI1 in cancer cells. Specific Aim 3. Examine the cellular functions of FAL1 in cancer initiation and progression.

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