癌症表达谱数据分析及癌症相关的长链非编码RNA LncRNA19功能机制的研究

Long noncoding RNAs (lncRNAs) have been demonstrated to be involved in various types of cancers. And rapidly growing evidence has shown that lncRNAs could serve as potential diagnostic biomarkers and therapeutic targets. Mitochondria are semi-automous organelle which plays a central role in cell metabolism and apoptosis. Abnormal proliferation and apoptosis are the classical cancer hallmarks, however, it depends on the mitochondria to provide sufficient energy for the infinite proliferation. At the same time, mitochondria could regulate cell death through inner or outer pathway. At present, there is no related research report about how lncRNA participate in mitochondrial pathway of apoptosis in cancer. Our preliminary study identified a long noncoding RNA named LncRNA19 by cancer microarray analysis, and our data showed that LncRNA19 could accelerate cell proliferation and repress cell apoptosis, LncRNA19 participate in mitochondrial pathway of apoptosis through interaction with E2F1. This proposal plan to confirm the regulation of LncRNA19 in proliferation and apoptosis, to explore the molecular mechanism of LncRNA19 in mitochondrial apoptosis pathway, and to construct the regulatory networks of cancer combined with the microarray and high-throughput sequencing data. By carrying out this study, we may offer new biomarkers and therapeutic targets for various types of cancers.

长链非编码RNA已被证实参与多种癌症的发生发展，癌症中异常表达的长链非编码RNA常被鉴定为癌症的标志物和治疗靶标。线粒体是半自主性细胞器，在细胞代谢和凋亡通路中发挥重要作用，癌症的主要特征是癌细胞无限增殖和凋亡异常，而癌细胞的增殖生长，需要线粒体提供能量，同时线粒体又能够通过内源或者外源的途径调控癌细胞凋亡，目前，lncRNA参与癌细胞线粒体的凋亡调控还没有相关报道。本研究通过癌症芯片表达谱数据，鉴定了一条癌症中表达上调的全新的lncRNA LncRNA19，初步研究发现，LncRNA19在癌细胞中能够促进增殖、抑制凋亡，并与E2F1结合参与癌细胞线粒体凋亡通路。在此基础上，我们将进一步明确LncRNA19在癌细胞增殖凋亡调控中的作用，探明LncRNA19与E2F1复合物在线粒体凋亡通路中的分子机制，并结合表达谱和高通量数据构建癌症调控网络，为癌症的诊断和治疗提供新的标志物和治疗靶标。