KRT19与肝细胞肝癌预后相关，但其参与肝癌发展的机制尚不明确。本研究结合前期成果进一步探索与KRT19相结合的非编码RNA在肝癌中的作用及机制。结合RIP及芯片发现，Linc504928与KRT19存在直接结合，细胞实验发现其能通过抑制KRT19丝/苏氨酸磷酸化促进肝癌细胞增殖。研究推测Linc504928可能通过抑制KRT19 Ser35磷酸化从而促进肝癌发展。研究拟通过沉默/过表达Linc504928细胞实验、动物模型及临床随访验证其作用；其次，通过磷酸化位点突变等鉴定Linc504928是否可结合并抑制KRT19 Ser35位点磷酸化；最后探明磷酸化KRT19下游可能的TGF-β1或NOTCH1信号通路。鉴于Linc504928及KRT19磷酸化在肝癌增殖中作用机制未有报道，本研究创新性的探究了Linc504928/p-KRT19调控网络，也为肝癌增殖机制研究提供了新的思路。

Keratin 19 has been proved to play a key role in the invasion of human hepatocellular carcinoma (HCC), however the detailed mechanism of the regulation of KRT19 still remained unclear. Based on our published results and gene chip, we aimed to investigate the function of lncRNA in regulating HCC cell proliferation by binding KRT19. Preliminary study and forecast results indicated Linc504928 could bind KRT19 directly and promoting tumor cell proliferation by declined the KRT19 phosphorylation level (serine/ threonine), we speculate the Ser35, a phosphorylation site on KRT19, may be the target. In this research, the function of Linc504928 will be first explored by clinical follow up, the gain/loss assay in vitro (liver cell lines) and in vivo (subcutaneously transplanted tumor). Secondly the point mutation, RNA pull-down assay and cell proliferative assay will be employed to determine whether Linc504928 could competitive inhibition the KRT19 phosphorylation on Ser35 site. Finally we plan to seek the signaling pathways downstream of Linc504928/p-KRT19 by TGF-β1 and (or) NOTCH1. Since Linc504928 and the KRT19 phosphorylation has not been reported in HCC, our study is an original source of innovation and may provide new idea for the research and treatment of HCC.