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（由申请人提供）：人类 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，这是一种侵袭性致命疾病，其特征是病毒感染的 CD4+ 克隆扩增T细胞。据估计，全世界有 20 至 3000 万人感染 HTLV-I。 ATL 是预后最差的疾病之一，急性期的中位生存期为 6-9 个月，淋巴瘤期的中位生存期为 10-12 个月。总体而言，接受各种化疗或放疗方案治疗的 ATLL 患者的生存率有限，因为大多数患者会因侵袭性肿瘤复发并很快死亡。 HTLV-I 肿瘤发生的分子基础尚不清楚。该疾病发病前的低发病率和长潜伏期表明，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-124a 在 ATL 细胞中通过其启动子的表观遗传沉默而被特异性下调。在本提案中，我们将进一步表征 miR-124a 对 HTLV-I 感染细胞增殖和存活的作用。然后我们将研究 HTLV-I 转化细胞中 miR-124a 和其他失调的 microRNA 之间的潜在合作。由于 miR-124a 在许多人类癌症中下调，因此该提议具有广泛影响的潜力。