hsa-miR-623对Ku80表达的调控及其对肺癌恶性生物学特征和肺癌放化疗敏感性的影响

项目名称： hsa-miR-623对Ku80表达的调控及其对肺癌恶性生物学特征和肺癌放化疗敏感性的影响

项目编号： No.81201848

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 肿瘤学2

项目作者： 魏双

作者单位： 华中科技大学

项目金额： 23万元

中文摘要： 多项研究表明DNA损伤感应分子Ku80在肺癌组织中的表达明显上调，且Ku80表达上调被证实与肺癌对放射线和化疗药物抵抗密切相关。但Ku80在肺癌中表达上调的分子机制目前尚无研究报道。我们的前期研究首次发现hsa-miR-623可呈剂量依赖性显著抑制Ku80蛋白的表达和肺癌细胞的增殖，且hsa-miR-623在人肺癌组织中的表达水平与癌周组织相比明显减低。这些结果表明hsa-miR-623表达下调可能是导致肺癌组织中Ku80表达上调的原因。该课题将深入研究hsa-miR-623对Ku80的调控作用，以及hsa-miR-623对肺癌细胞增殖、迁移和侵袭等恶性生物学特征的影响，并在体内外的实验中研究hsa-miR-623对肺癌的抑制作用以及联合放化疗对肺癌的治疗价值。该研究将揭示hsa-miR-623在肺癌发生发展中的作用及其对肺癌放化疗敏感性的影响，为提高肺癌的治疗效果提供新途径。

中文关键词： hsa-miR-623；Ku80；非小细胞肺癌；增殖；转移

英文摘要： DNA damage sensor Ku80 expression had been shown to be significantly increased in lung cancer tissue, and Ku80 upregulation was significantly correlated with the resistance to radiation and drug in lung cancer. However, the mechanism of Ku80 upregulation in lung cancer has not been understood. Our previous study firstly indicated that hsa-miR-623 significantly suppressed Ku80 expression and the lung cancer cell proliferation in a dose-dependent manner, and hsa-miR-623 expression was significantly decreased in lung cancer compared with that in adjacent lung tissue. These data implicated that hsa-miR-623 dysregulaion might be the cause of Ku80 upregulaion in lung cancer. We will further investigate the regulatory effect of hsa-miR-623 on Ku80 gene and its effects on malignant biological characteristics of lung cancer, as well as the tumor suppressive role of hsa-miR-623 and therapeutic effects of hsa-miR-623 combined chemoradiotherapy in lung cancer. This study will reveal the important role of has-miR-623 in pathogenesis and development and its effect on the chemoradiotherapy sensitivity of lung cancer, which will provide a new approach of improving the therapeutic effect of lung cancer.

英文关键词： hsa-miR-623；Ku80；NSCLC；proliferaiton；metastasis