新基因C20orf108在卵巢癌顺铂化疗耐药中的机制研究

The incidence rates of ovarian cancer are highest in the Western world, which is the leading cause of death from gynecological malignancies. Because of subsequent relapse following the development of chemotherapy resistance, a better understanding of the mechanisms underlying chemotherapy resistance and improving the sensitivity of ovarian cancer to chemotherapy treatment play an important role in reversing treatment inefficiency. However, the mechanisms underlying chemotherapy resistance have not been established, and it led to marginal improvements in the survival of patients. C20orf108 is a new gene screened from previous study, which function is unknown and rarely reported. We have found that in ovarian cancer, the mRNA level is lower than in ovarian normal tissue, and it interacts with BCL-2 family pro-apoptotic protein Bim to induce abnormal apoptosis which is the main mechanism of ovarian cancer resistance to chemotherapy. Using the SMART, molecular biology and laser scanning cytometry, the project intend to systematically study the structure and function of new gene C20orf108 from cell biological, molecular and overall aspects, and reveal the role of C20orf108 in ovarian cancer and other solid malignancies, providing theory and new molecular target for reversing ovarian cancer chemoresisitance.

卵巢癌是最常见的妇科肿瘤之一,死亡率居妇科肿瘤之首，而化疗耐药是预后不佳的重要因素之一。因此揭示卵巢癌化疗耐药的机制，提高卵巢癌化疗的敏感性是扭转现阶段卵巢癌治疗效果差的关键。然而卵巢癌化疗耐药的机制目前尚不明确，使得该领域进展缓慢。C20orf108是项目申请人在前期研究中运用文库筛选技术获取的新基因.对其功能鲜有报道。前期研究我们发现与正常组织相比此基因在卵巢癌组织表达下降，并且通过BCL-2家族的蛋白Bim使得肿瘤细胞凋亡机制异常从而导致对顺铂化疗耐药。本项目拟从细胞，分子，整体三个层次入手，运用文库，分子生物学和切片流式定量分析技术，全面研究新基因C20orf108的结构及功能，揭示其参与卵巢癌耐药的发生机制，并进一步探讨此基因在其它实体性肿瘤耐药中的作用，为卵巢癌化疗耐药逆转提供新的分子靶点和理论依据。

卵巢癌是最常见的妇科肿瘤之一,死亡率居妇科肿瘤之首，而化疗耐药是预后不佳的重要因素之一。因此揭示卵巢癌化疗耐药的机制，提高卵巢癌化疗的敏感性是扭转现阶段卵巢癌治疗效果差的关键。然而卵巢癌化疗耐药的机制目前尚不明确，使得该领域进展缓慢。FAM210B是项目申请人在前期研究中运用文库筛选技术获取的新基因，对其功能鲜有报道。本项目从细胞，分子，整体三个层次入手，运用文库，分子生物学和切片流式定量分析技术，首次明确FAM210B的细胞定位、调节细胞能量代谢的方式及参与卵巢癌顺铂化疗的调控机制。FAM210B定位于线粒体内膜上，通过调节丙酮酸脱氢酶激酶（PDK4）的活性从而调控线粒体能量代谢，改变卵巢恶性肿瘤细胞代谢的方式，导致对顺铂的化疗耐药。本项目从功能效应的角度，系统、有的放矢的研究FAM210B与卵巢癌顺铂化疗耐药逆转效应的科学问题，为晚期化疗耐药的卵巢癌的临床治疗开辟一条新的探索途径。