循环非编码RNA调控肿瘤免疫微环境中TRAF6/NF-κB网络在肝癌进展中的作用机制研究

肝癌作为威胁我国人民健康的重大疾病，其高侵袭性、高转移性是影响疗效和患者长期生存的主要原因。通过针对肿瘤免疫微环境中免疫细胞的多谱系、多人群标本的高通量测序，我们筛选出与肝癌转移密切相关的循环非编码RNA：miR-194，LncRNA ACDH2.1和LncRNA AC011239.1。初步研究提示，在他们的共同调控下，免疫细胞内的TRAF6/NF-κB通路得以激活，并影响肿瘤细胞的增殖，转移。但目前对于循环非编码RNA调控免疫细胞的研究尚未见诸报道。因此，本项目拟利用大量临床标本验证循环非编码RNA对其靶基因网络化调控机制，并揭示肿瘤免疫微环境与肝癌转移的关系。同时，本研究也将筛选循环中稳定非编码RNA或其降解产物并探讨其作为预测肝癌转移早期指标的可能性。综上，本项目旨在进一步阐明肝癌发生转移的分子机制，筛选早期预测肝癌转移的标记物，也为寻找新的治疗靶点提供依据。

Hepatocellular carcinoma (HCC) by means of its highly invasive and metastatic biological characteristics became the main disease affecting the treatment efficacy and long-term survival of patients in China. .By using the multi-genealogy specimen and high throughput sequencing technology on the immune cells in tumor immune micro environments (TIME), we have screened out three tumor metastasis related molecules which are miR-194，LncRNA ACDH2.1 and LncRNA AC011239.1 in immunocytes. We found that, through the non-coding RNA network, TRAF6/NF-κB signaling could significantly upregulated and augmented HCC cell line invasion can also be observed..Since the exact mechanism that non-coding RNA regulating down-streams signaling and its impact on HCC metastasis are unclear, in this study, large scale analysis of HCC specimen will be involved to determine the correlation between immunocytes and HCC metastasis. Various models will be established to verify the mechanism of non-coding RNA affecting immunocytes activity. At the same time, the molecular basis underlying the circulating non-coding RNA associated metastasis will be investigated. Moreover, degradation products will be analyzed in the peripheral blood and its potential of early-predicting HCC metastasis will be explored..In conclusion, clarification of the mechanism underlying non-coding RNA network induced immunocytes dysfunction and its impact on HCC progress will be benefit for better understand HCC progression and lying theoretical basis for developing novel predicting markers and treatment targets.