长链非编码RNA SGOL1-AS1下调在胃癌细胞增殖及染色体不稳定性中的作用及其机制

lncRNA在肿瘤的发生、发展中起着重要作用。本课题组前期发现：反义lncRNA SGOL1-AS1在胃癌中显著下调；下调SGOL1-AS1促进胃癌细胞增殖、诱导G2/M期阻滞；SGOL1-AS1负调控正义编码基因SGOL1表达；MYC活化SGOL1及反义链SGOL1-AS1启动子；SGOL1-AS1表达受甲基化调控。本项目拟证实MYC激活SGOL1及SGOL1-AS1转录；研究SGOL1-AS1是否阻断MYC诱导的SGOL1基因转录；阐明SGOL1-AS1是否影响SGOL1 mRNA稳定性；阐明胃癌SGOL1-AS1下调机制及其下调在胃癌细胞增殖、有丝分裂及CIN中的作用；研究SGOL1-AS1及SGOL1的临床意义。上述研究将阐明SGOL1-AS1的生物学功能及MYC/SGOL1-AS1/SGOL1调控机制，可望为阐明胃癌发病机制提供新的依据，并有望为胃癌预后判断提供新的标志物。

lncRNAs have been shown to play pivotal roles in tumorigenesis and tumor progression. Our recent data demonstrated that antisens lncRNA SGOL1-AS1 was significally down-regulated in compared with matched normal tissues. Functional studies revealed that SGOL1-AS1 knockdown promoted GC cell proliferation and increased the cells of G2/M phase. We further revealed that SGOL1-AS1 negatively regulated SGOL1 expression, while MYC transactivated both SGOL1 and SGOL1-AS1. In addition, SGOL1-AS1 was regulated by DNA methylation. Based on these preliminary results, we will first validate MYC-induced transcription of both SGOL1 and SGOL1-AS1. Then, we will determine whether SGOL1-AS1 blocks MYC-mediated SGOL1 transcription and influences SGOL1 mRNA stability. The third, we will investigate the mechanism of SGOL1 down-regulation in GC and the effects of its downregulation on cell proliferation,mitosis and chromsome instability (CIN). The corrections between SGOL1-AS1/SGOL1 and clinical characteristics including GC prognosis will also be investigated. In conclusion, our current study is designed to clarify the function of SGOL1-AS1 and to investigate reciprocal regulation of MYC, SGOL1-AS1 and SGOL1 in GC. It will provide the new evidences to clarify the mechanisms of GC pathogenesis and develop valuable markers of gastric cancer prognosis.