核受体NR1H3对膀胱癌生物学行为的调控及其机制研究

Bladder cancer (BC) is the most common urinary tumors in China. Patients suffer a lot of physical, psychological and economic burdens because of high recurrence rate and long term treatment. Previous evidence showed that ectopic expression of nuclear receptors are related with both prognosis and treatment of several kinds of malignant tumors. Our previous work scaned all the 48 nuclear receptors of homo sapiens in TCGA database. After large population validation in our center, low expression of NR1H3 was confirmed to be related with poor prognosis of bladder cancer. Interestingly, NR1H3 could interact with LOC572558 which was proved to be a tumor suppresser in bladder cancer through Akt-MDM2-p53 pathway. Therefore, we hypothesis that NR1H3 inhibit bladder cancer progression through modulating lncRNA LOC572558. This project would reveal the mechanism of BC tumorigenesis and progressiveness by studying the role of NR1H3 and LOC572558. It is meaningful for the understanding of bladder cancer theoretically and practically. The project may shed light of the treatment of bladder cancer management with important scientific interest and clinical application.

膀胱癌是我国最常见的泌尿生殖系统恶性肿瘤，易复发，治疗时间长，患者经济负担重。以往证据表明核受体的差异化表达与多种肿瘤的治疗和预后相关。本课题组前期工作通过TCGA数据库筛选所有的人类48种核受体，并通过本中心大样本的人群验证，发现膀胱癌中NR1H3表达降低，且与膀胱癌的不良预后相关。并且NR1H3与长链非编码RNA LOC572558具有相互作用。而在我们的前期研究中，长链非编码RNA LOC572558可以通过Akt-MDM2-p53通路抑制膀胱癌增殖。据此我们提出假设，核受体NR1H3通过与长链非编码RNA LOC572558的交互作用参与了膀胱肿瘤的发生和进展。本课题拟通过研究NR1H3对LOC572558的调控作用，揭示NR1H3对膀胱癌的作用机制。为揭示膀胱癌的发生提供理论和实验基础。本课题有望为治疗膀胱肿瘤和预防复发提供新靶点，具有重要的科学意义和临床应用价值。

膀胱癌是我国最常见的泌尿生殖系统恶性肿瘤，易复发，治疗时间长，患者经济负担重。以往证据表明核受体的差异化表达与多种肿瘤的治疗和预后相关。本课题组前期工作通过TCGA数据库筛选所有的人类48种核受体，并通过本中心大样本的人群验证，发现膀胱癌中NR1H3表达降低，且与膀胱癌的不良预后相关。并且NR1H3与链非编码RNA LOC572558具有相互作用。而在我们的前期研究中，长链非编码RNA LOC572558可以通过Akt-MDM2-p53通路抑制膀胱癌增殖。据此我们提出假设，核受体NR1H3通过与长链非编码RNA LOC572558的交互作用参与了膀胱肿瘤的发生和进展。本项目主要由体内外试验来研究 NR1H3在 BLCA中的抑制作用，通过对 TCGA数据库分析发现，NR1H3和 LOC572558的表达具有正相关的关系。通过Chip，Luciferase和pull-down的方法证实了NR1H3和 LOC572558在细胞中的相互作用。