中文摘要
lncRNAs与肝细胞癌(HCC)术后复发转移的相关性值得亦有待深入研究。课题组前期研究发现HCC中lncRNA TMPO-AS1表达上调;与肝癌根治术后复发显著相关;基因敲减后显著抑制肿瘤细胞克隆形成及转移;异常表达的TMPO-AS1与TGFβ通路异常激活紧密相关,而TGFβ通路在肝癌发展中起抑癌和促癌双向作用。我们认为肝组织中表达上调的TMPO-AS1调控TGFβ通路向促癌方向转化,进而促进肝癌术后复发转移。为此,本研究拟进一步扩大病例数并结合临床表型,明确TMPO-AS1与HCC临床相关性;正负向干预TMPO-AS1表达,通过体内外功能实验证实并发掘促癌作用;应用TGFβ通路激活剂、抑制剂结合EMSA、RNA-pull down、RIP等技术明确TMPO-AS1调控TGFβ通路的分子机制。旨在探讨长链非编码RNA TMPO-AS1作为肝癌发展的新作用分子,为临床诊疗提供新靶点。
英文摘要
The relationship between lncRNAs and hepatocellular cancer recurrence after radical resection deserves further study. Our previous study found that lncRNA-TMPO-AS1 upregulated in HCC, and the factor showed significant correlation in recurrence after liver cancer radical resection. Meanwhile the knockdown of lncRNA-TMPO-AS1 was proved significantly inhibiting tumor cell colony formation and metastasis, as well as the abnormal expression of TMPO-AS1 is closely related to abnormal activation of TGFβ signal pathway. TGFβ pathway plays a two-way role of tumor suppressor and promoter in the development of liver cancer. We believe that the TMPO-AS1 upregulated TGFβ pathway in liver tissue to promote liver tumor progression, thus contributing to liver cancer recurrence and metastasis. Therefore, this study intends to further clear the role of TMPO-AS1 in HCC clinical relevance by using clinical samples and information; by positively and negatively intervening the TMPO-AS1 expression, as well as functional experiments to confirm and explore its tumor promotion. Then we intend to apply the TGFβ pathway activator and inhibitor compounded with EMSA, RNA-pull down, RIP technology to clear TMPO-AS1 molecular regulating mechanisms in TGFβ pathway. In summary, this study is designed to investigate the long non-coding RNA-TMPO-AS1 as a new molecule in the development of liver cancer, and providing it as a new targets for clinical diagnosis and treatment.
