线粒体内膜蛋白C11orf83稳定HIF-1α促进肝癌生长的作用机制研究

HIF-1α plays an important role in the growth and progression of malignant liver cancer, but now the mechanism of stabilizing HIF-1α under hypoxia is not fully understood. C11orf83 is a newly identified as a component of mitochondrial respiratory chain complex III. We found that C11orf83 is high-expressed in hypoxic liver cancer cells and can tumor cells survival and proliferation. However, cells viability significantly decreased when the expression of C11orf83 expression is down-regulated. Furthermore, the expression of HIF-1α also markedly decreased. We believe that the up-regulation of C11orf83 and stabilizing HIF-1α is a self-protection mechanism of liver cancer cells during hypoxia. In this project, we will focus on the biological role of C11orf83 under hypoxic conditions in liver cancer cells, the role of C11orf83 in the mitochondrial respiratory chain, and molecular mechanisms of C11orf83 stabilizing HIF-1α. This project will reveal the role and mechanism of mitochondrial respiratory chain in promoting liver cancer growth, and open a new window for the treatment of liver cancer.

HIF-1α在肝癌的生长及恶性进展过程中发挥着重要作用，然而目前对于HIF-1α在低氧细胞中稳定的分子机制还不是非常清楚。C11orf83是新鉴定的一个线粒体呼吸链复合物III组成蛋白，定位于线粒体内膜。我们发现C11orf83在低氧的肝癌细胞中高表达，并促进肝癌细胞在低氧环境下的存活和增殖，而干扰C11orf83会显著降低HIF-1α的表达及肝癌细胞的存活能力。因此我们认为，C11orf83的反馈性上调并稳定HIF-1α是肝癌细胞在低氧时启动的自我保护机制之一。本项目中，我们将重点研究低氧条件下C11orf83在肝癌细胞中的生物学作用、C11orf83表达上调后对线粒体呼吸链的作用、以及C11orf83稳定HIF-1α的分子机制。本项目的实施将进一步揭示线粒体呼吸链在促进肝癌生长过程中的作用及机制，有可能为肝癌的治疗提供新思路，具有很好的创新性、学术意义和潜在应用前景。