hsa_circRNA_104515竞争性结合miR-1303调控PLIN1在肝细胞癌发生发展中的作用及机制研究

hsa_circRNA_104515, a novel circular RNA, which function in carcinoma remains unclarified. We found previously that the expression of hsa_circRNA_104515 was significantly lower in Hepatocellular Carcinoma (HCC), while miR-1303 was significantly highly expressed in HCC. Additionally, bioinformatics prediction showed that there was a conservative binding site between mir-1303 and hsa_circRNA_104515. On the other hand, we combined multiple algorithms to predict that PLIN1 was a potential target gene for mir-1303, which we previously found up-regulated in HCC samples, and the expression of PLIN1 was associated with the prognosis of HCC. Therefore, we hypothesize that hsa_circRNA_104515 may regulate PLIN1 expression via sponging miR-1303 and then, play a vital role in the hepatocarcinogenesis and development of HCC. In the current study, we plan to verify the relationships of hsa_circRNA_104515, miR-1303 and PLIN1 and to investigate their molecular mechanisms of regulation on the hepatocarcinogenesis and development in vitro and in vivo by using RT-qPCR, in situ hybridization, cell transfection, RNA interference, chicken embryochorioallantoic membrane and nude mouse models.

hsa_circRNA_104515是新发现的环状RNA,与肿瘤的关系尚未见文献报道。前期发现hsa_circRNA_104515在肝细胞癌(HCC)中低表达，miR-1303在HCC组织中显著高表达，生物信息学预测提示miR-1303与hsa_circRNA_104515存在保守的结合位点。另外，我们联合多种算法预测PLIN1是miR-1303的潜在靶基因，且该基因在HCC中显著高表达，并与HCC预后呈负相关。据此推测hsa_circRNA_104515可能扮演miR-1303海绵，通过调节PLIN1水平对HCC的发生发展发挥作用。本项目拟在前期基础上通过 real time RT-qPCR、原位杂交、细胞转染、RNA干扰，CAM和裸鼠等体内、体外模型，多角度的探讨hsa_circRNA_104515、miR-1303及PLIN1之间的靶向关系及对HCC发生发展作用的分子机制。

hsa_circRNA_104515是新发现的环状RNA,与肿瘤的关系尚未见文献报道。前期发现hsa_circRNA_104515在肝细胞癌(HCC)中低表达，miR-1303在HCC组织中显著高表达，生物信息学预测提示miR-1303与hsa_circRNA_104515存在保守的结合位点。另外，我们联合多种算法预测PLIN1是miR-1303的潜在靶基因，且该基因在HCC中显著高表达，并与HCC预后呈负相关。据此推测hsa_circRNA_104515可能扮演miR-1303海绵，通过调节PLIN1水平对HCC的发生发展发挥作用。本项目拟在前期基础上通过 real time RT-qPCR、原位杂交、细胞转染、RNA干扰，鸡胚尿囊膜和裸鼠等体内、体外模型，多角度的探讨hsa_circRNA_104515、miR-1303及PLIN1之间的靶向关系及对HCC发生发展作用的分子机制。