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MicroRNAs in Human Ovarian Cancer

人类卵巢癌中的 MicroRNA

基本信息

批准号：
8257530
负责人：
Jin Q Cheng
金额：
$ 33.61万
依托单位：
H. LEE MOFFITT CANCER CTR & RES INST
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-06-01 至 2014-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8257530
关键词：
Apoptosis Behavior Cancer Patient Cancerous Cause of Death Cell Culture Techniques Cell Proliferation Cell Survival Cell physiology Characteristics Clinical Data Death Rate Development Diagnosis Diagnostic Disease Down-Regulation Early Diagnosis Ectopic Expression Epithelial Cells Gene Targeting Genes Goals Growth Human Intervention Intra-abdominal Lead Lysophospholipids Malignant - descriptor Malignant Neoplasms Malignant neoplasm of ovary Messenger RNA Metastatic Malignant Neoplasm to the Ovary MicroRNAs Molecular Profiling Neoplasm Metastasis Normal Cell Nucleotides Oncogenes Oncogenic Operative Surgical Procedures Ovarian Ovarian Carcinoma Ovary Patients Phenotype Plasma Platinum Play Primary Neoplasm Process Prognostic Marker Receptor Gene Regulation Relapse Resistance Role Scheme Screening for Ovarian Cancer Serum Simian virus 40 Small RNA Staging Surface Survival Rate Testing Tissues Transcriptional Regulation Transgenic Mice Treatment Failure Tumor Debulking Tumor Markers Tumor Suppressor Genes Up-Regulation Western World Xenograft procedure angiogenesis base cancer cell cancer therapy carcinogenesis cell motility chemotherapy epithelial to mesenchymal transition gain of function loss of function lysophosphatidic acid malignant phenotype mouse model mullerian-inhibiting hormone neoplastic novel outcome forecast overexpression promoter response standard care therapeutic target tumorigenesis

项目摘要

Ovarian carcinoma is the leading cause of death from gynecological malignancies in the western world. Its high death rate is a result of the fact that most patients (~75%) are diagnosed at an advanced stage of disease with disseminated intra-abdominal metastasis. Debulking surgery followed by platinum-based chemotherapy schemes is considered standard care for these patients. However, despite an initial response rate of 65%-80% to first-line chemotherapy, most ovarian carcinomas relapse. Acquired resistance to further chemotherapy is generally responsible for treatment failure, resulting in an overall 5-year survival rate of only about 25% for late- stage ovarian cancer. Thus, there is urgent need to identify novel molecules that are responsible for chemoresistance and ovarian cancer development, and thus lead to new targeted therapy. MicroRNAs (miRNA) are a class of small RNAs that are phylogenetically conserved and play important roles in the regulation of cell survival, proliferation, differentiation and angiogenesis. Accumulated studies shows that miRNAs are frequently deregulated in human malignancy and function as either "oncogenes" or "tumor suppressor genes". In addition, miRNA expression signatures correlate well with specific clinical cancer characteristics and can be used to classify normal and cancerous tissues as well as subtype of malignancy. Our preliminary data show frequent upregulation or downregulation of miRNAs in human ovarian cancer, some of which, especially miR-214, are involved in chemoresistance and metastasis and have oncogenic activity. Based on these preliminary data and the fact that each miRNA negatively regulates hundreds of genes, we hypothesize that miRNAs play significant role in ovarian carcinogenesis, intra-abdominal dissemination and chemoresistance and could be therapeutic targets for human ovarian cancer. Thus, the objective of this project is to determine the miRNAs as pathogenetic factors and therapeutic targets in ovarian cancer. To test our hypothesis and achieve our goal, we will 1) determine the mechanism of overexpression of miR-214 in ovarian cancer; 2) examine the effects of miR-214 gain- and loss-of-function on the neoplastic phenotypes of ovarian cancer cells and the oncogenic activity of miR-214 in OSE cells; 3) determine the consequence of miR-214 gain of function on ovarian tumorigenesis in transgenic mice and 4) validate the miR-214 targeted genes and determine the mechanism of miR-214 in oncogenesis.

卵巢癌是西方国家妇科恶性肿瘤死亡的主要原因。其高