肝细胞癌（HCC）转移是导致患者死亡的主要原因。间质-上皮转化（MET）在肿瘤转移灶形成中起关键作用。有研究显示配对相关同源盒1（Prrx1）的下调是肿瘤MET和转移灶形成的必要条件之一，但机制不清。我们初步研究表明HCC组织中Prrx1低表达者更易出现复发转移；Prrx1可能通过与配对样同源盒2（Pitx2）的相互作用调控miRNA进而参与MET，TGFBR2和Slug的抑制可能是其下游分子机制。在此基础上，我们预备在分子、细胞、动物及临床水平进一步明确：Prrx1下调是否通过Pitx2-miRNA调节HCC的MET并促进转移灶形成；Prrx1与Pitx2相互作用方式及调控MET的分子机制；Prrx1/ Pitx2 和关键 miRNA 与HCC预后的相关性。有望首先揭示Prrx1/Pitx2在HCC的MET和转移灶形成中的作用和机制，为HCC复发转移的诊治和预后判断提供新的靶点和标志物。

Metastasis is the most common cause of death in patients with hepatocellular carcinoma (HCC). Mesenchymal-epithelial transition (MET) plays a vital function in the process of metastasis formation. Studies have shown that the down-regulation of paired related homeobox 1(Prrx1) is necessary for MET happening, whose mechanism is still unclear. Our preliminary study shows that HCC with lower Prrx1 expression are likely to relapse and form metastasis. The down-regulation of Prrx1 induces MET in HCC cells and increases the expression of paired-like homeobox2 (Pitx2).The simultaneous interfering of Pitx2 expression reverses Prrx1 down-regulation–induced MET. The co-immunoprecipitation result reveals a direct interaction between Prrx1 and Pitx2. It is reported that Pitx2 can be involved in MET process by regulating multiple miRNAs, suggesting that Prrx1 might regulate the MET in HCC cells through Pitx2-miRNA pathway, the mechanism of which might be the inhibition of tumor growth factor beta receptor 2 (TGFBR2) and the EMT transcription factor Slug. On this basis, we aim to investigate the following problems in the level of molecular, cell, animal and clinical specimens: Whether the down-regulation of Prrx1 could induce MET in HCC cells and promote metastasis formation through Pitx2-miRNA pathways? What is the specific interaction between Prrx1 and Pitx2 and what is the detailed mechanism underlying induced MET? Whether the expression of Prrx1 could predict the prognosis of HCC patients? This study is expected to reveal the function of Prrx1/Pitx2 in HCC cell MET and metastasis formation as well as the underlying mechanism, which will provide a novel marker for predicting the relapse, metastasis and prognosis of HCC and offer theoretical basis for the development of new treatment methods.