中文摘要
结直肠癌(CRC)是最常见的恶性肿瘤之一,至今未充分阐明其发病机制。申请者前期研究发现,长链非编码RNA MIR22HG在CRC组织中下调,且过表达MIR22HG能够抑制CRC细胞体外生长和迁移能力,提示其可能是一个新的抑癌基因。RNA-pulldown和RIP实验发现MIR22HG直接绑定SMAD2来抑制CRC细胞生长与转移。本项目拟在此基础上,应用细胞分子生物学、实验动物学等手段从体外细胞水平及活体水平进一步研究MIR22HG对CRC细胞恶性表型及癌变相关的细胞生命活动的影响。进一步研究其调控的信号通路,以阐明MIR22HG调控CRC发生发展的分子机制。结合临床标本,分析MIR22HG和CRC患者预后及临床病理表型的关系,评估MIR22HG表达在指导治疗、判断预后中的临床应用价值。研究结果为解释CRC的发病机制及防治提供新的理论和实验依据,并为CRC 的诊断、治疗和预后提供重要指导。
英文摘要
Colorectal cancer (CRC) is one of the most common malignant tumors, and the molecular mechanism of CRC is poor elucidated. Our previous studies found that MIR22HG was significantly down-regulated in CRC tissues, and overexpression of MIR22HG inhibited the proliferation and migration of CRC cells, suggesting that MIR22HG is a new CRC-related potential tumor suppressor genes. Through the RNA-pulldown and RIP found MIR22HG can directly binding SMAD2 protein to suppress the growth and metastasis of CRC cells Based on these new findings, the present project plans to further evaluate the effects of MIR22HG on the CRC-related malignant phenotypes from in vitro and in vivo levels using experimental methods of cellular, molecular biology and experimental zoology. In order to clarify the mechanism of MIR22HG regulating the development and progression of CRC, we will explore the MIR22HG-related signaling pathways. In addition, this project plans to analyze the relationship between the MIR22HG expression in CRC tissues and the prognosis or clinical pathological features of CRC, and to further evaluate the application value of MIR22HG in guiding treatment and judging prognosis. The results could provide new theoretical and experimental data for the pathogenesis, prevention and therapy of CRC, and also provide an important guidance for the diagnosis, treatment and prognosis of patients with CRC.
