肿瘤相关巨噬细胞(TAMs)可增强肝细胞肝癌(HCC)侵袭性，前期研究发现其可通过下调TGFBR2上调和ACVR1的表达，引起TGF-β1/BMP-7失衡。差异microRNA分析显示miR-17-92 cluster在失衡组显著升高，其可直接干扰TGFBR2转录和表达；却仅上调ACVR1蛋白，提示存在翻译后调控。泛素化调节是ACVR1翻译后调控的重要机制，Smurf1是ACVR1泛素化降解的关键分子，并与miR-17-92 cluster多个成员存在潜在靶向结合，提示miR-17-92 cluster可通过干扰Smurf1调控ACVR1表达。故本研究拟从泛素化失调角度，探讨miR-17-92 cluster在TAMs诱导TGF-β1/BMP-7失衡中关键作用，阐明其上调ACVR1的分子机制，观察靶向阻断MIR17HG和ACVR1后的疗效，为HCC筛选新治疗靶点。

Tumor-associated macrophages (TAMs) promote cell aggressiveness in hepatocellular carcinoma (HCC). In our previous study, we found that TAMs induced HCC phenotypic transformation, featured as TGF-β1/BMP-7 imbalance in HCC cells, and thus promoted HCC invasion. Differential microRNA analysis shows miR-17-92 cluster significantly increased in TGF-β1/BMP-7 imbalance group. And miR-17-92 cluster inhibits TGFBR2 transcription by binding to its 3'UTR. But it increases ACVR1 exclusively at protein level, which implied it is post-translational modification. Ubiquitination is one of the most important post-translational regulation manner. Smurf1 is the key molecular event for ubiquitination degradation of ACVR1 protein. Previously it has been predicted that miR-17-92 cluster has potential binding sites to Smurf1 3'UTR by TargetScan software. Therefore, this study intends to investigate the key mechanism involved in miR-17-92cluster induced up-regulation of ACVR1 protein from the perspective of ubiquitination imbalance, in order to clarify specific mechanism of TAMs-induced TGF-β1/BMP-7 imbalance in HCC. Furthermore, we intend to explore the potential therapeutic significance of targeting MIR17HG and ACVR1 in order to screen valuable candidates for HCC therapeutic targets.