中文摘要
转移是胃癌患者预后差的重要原因,但其机制未明。课题组前期研究发现:长链非编码 RNA MLLT4-AS1在胃癌中较正常组织低表达,且其表达与胃癌TNM分期、淋巴结转移呈显著负相关,可用于指示胃癌预后;MLLT4-AS1过表达的胃癌细胞体外侵袭转移能力下降。初步实验提示MLLT4-AS1有可能通过招募转录因子STAT3增强MLLT4表达,从而抑制胃癌转移。本课题拟扩大样本验证MLLT4-AS1和MLLT4作为胃癌转移及预后标志物的效果;通过体外实验和小鼠胃癌转移模型验证MLLT4-AS1和MLLT4抑制胃癌转移的功能;结合 RIP、ChIP等方法阐明MLLT4-AS1通过招募STAT3促进MLLT4表达,从而抑制胃癌转移的分子机制。本课题将为以MLLT4-AS1/MLLT4为靶点的胃癌精准治疗提供理论依据。
英文摘要
Metastasis is an important reason for gastric cancer patients’poor prognosis. However,the mechanism still remains unclear. Our previous research demonstrated that long non-coding RNA MLLT4-AS1 was low expressed in gastric cancer, which expression level showed a negative correlation with TNM stage, lymphatic metastasis and poor prognosis in gastric cancer tissues. Pre-experiment showed that overexpression of MLLT4-AS1 could decrease the invasive and metastatic capacity of gastric cancer cells. Primary results indicated that MLLT4-AS1might modulate the expression level of MLLT4 to repress gastric cancer metastasis by combining STAT3. In this research,We plan to evaluate the effectivity of MLLT4-AS1 and MLLT4 as the biomarkers of gastric cancer metastasis and prognosis through clinical trial, to explore the function of MLLT4-AS1 and MLLT4 facilitated gastric cancer metastasis by using cell lines and mouse model of gastric cancer, to definite the molecular mechanism that MLLT4-AS1 inhibits gastric cancer metastasis by promoting the expression of MLLT4 by STAT3 with RIP,CHIP and other methods. The research would provide MLLT4-AS1/MLLT4 as a novel target for diagnosis and treatment of gastric cancer.
