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Role of miR-124a in HTLV-I oncogenesis

miR-124a 在 HTLV-I 肿瘤发生中的作用

基本信息

批准号：
8287054
负责人：
CHRISTOPHE P NICOT
金额：
$ 16.31万
依托单位：
UNIVERSITY OF KANSAS MEDICAL CENTER
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：
2011-07-01 至 2013-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8287054
关键词：
Acute Adult Affect Apoptotic BCL2 gene Biological Biological Assay CD4 Positive T Lymphocytes Cell Cycle Cell Proliferation Cell Survival Cells Clonal Expansion Data Disease Disease Progression Down-Regulation Epigenetic Process Gene Targeting Genome Growth Human Human T-lymphotropic virus 1 Hypermethylation Incidence Infection Lymphoma Lymphomagenesis Lymphoproliferative Disorders Malignant Neoplasms Mediating MicroRNAs Molecular Mutation Oncogenic Onset of illness Outcome Pathogenesis Pathway interactions Patients Phase Process Radiation therapy Regimen Relapse Reporting Role STAT3 gene Site T-Cell Leukemia Viral Viral Genome Virus Virus Diseases Virus Replication base cell transformation cellular targeting chemotherapy human disease in vitro Assay leukemia metaplastic cell transformation new therapeutic target novel outcome forecast prognostic promoter small hairpin RNA tumor tumorigenesis vector

项目摘要

DESCRIPTION (provided by applicant): Human T-cell Leukemia Virus type 1 (HTLV-I) is the etiological agent of adult T-cell leukemia (ATL), an aggressive and fatal disease characterized by a clonal expansion of virus-infected CD4+T cells. It is estimated that 20 to 30 million people worldwide are infected with HTLV-I. ATL has one of the poorest prognoses, with a median survival of 6-9 months in the acute phase and 10-12 months in the lymphoma phase. Overall, survival of ATLL patients treated with various chemotherapy or radiotherapy regimens is limited, as most patients relapse with aggressive tumors and succumb shortly thereafter. The molecular basis of HTLV-I oncogenesis is not well understood. The low incidence and long latency before the onset of the disease suggest that accumulation of genetic alterations of host infected cells is required for disease progression. We have found that microRNA miR-124a is specifically down-regulated through epigenetic silencing of its promoter in ATL cells. In this proposal, we will further characterize the role of miR-124a on the proliferation and survival of HTLV-I infected cells. We will then study the potential cooperation between miR-124a and other microRNA deregulated in HTLV-I transformed cells. Since miR-124a is down regulated in many human cancers, this proposal has the potential for broad implications.

描述（由申请方提供）：人T细胞白血病病毒1型（HTLV-I）是成人T细胞白血病（ATL）的病原体，ATL是一种侵袭性和致命性疾病，其特征为病毒感染的CD 4 +T细胞的克隆扩增。据估计，全世界有2000万至3000万人感染HTLV-I。ATL是最差的预后之一，急性期的中位生存期为6-9个月，淋巴瘤期为10-12个月。总的来说，接受各种化疗或放疗方案治疗的ATLL患者的生存率是有限的，因为大多数患者复发侵袭性肿瘤并在此后不久死亡。HTLV-I肿瘤发生的分子基础还不清楚。发病率低和发病前潜伏期长表明，宿主感染细胞的遗传改变的积累是疾病进展所必需的。我们发现microRNA miR-124 a通过其启动子在ATL细胞中的表观遗传沉默而特异性下调。在这个提议中，我们将进一步表征miR-124 a对HTLV-I感染细胞的增殖和存活的作用。然后，我们将研究miR-124 a与HTLV-I转化细胞中其他失调的microRNA之间的潜在合作。由于miR-124 a在许多人类癌症中下调，因此该提议具有广泛的意义。