LncRNA UCHL1-AS1在人肝癌中的生物学作用及分子机制研究

UCHL1-AS1是一类新发现的反义长链非编码RNA(LncRNA)，文献报道其能促进与之互补的编码基因UCHL1转录后水平的表达，而UCHL1在人肝细胞癌中能抑制增殖、促进凋亡。我们前期工作发现，UCHL1-AS1在人肝癌组织及细胞株中处于低表达状态，并且其表达水平与门静脉癌栓相关。据此提出假说：UCHL1-AS1通过靶向作用于UCHL1而抑制肝癌的增殖、转移及促进凋亡。本课题将从临床组织标本、体外细胞、动物实验三个层面，采用qRT-PCR、原位杂交、Western blot、RNA干扰等手段，研究UCHL1-AS1在肝癌中的临床意义；UCHL1-AS1对肝癌细胞生物学功能的影响；UCHL1-AS1与UCHL1的靶向调控关系以及肝癌中UCHL1-AS1相关的抑癌机制，以阐明UCHL1-AS1在肝癌发生发展中的作用及机制，为临床诊治提供契机。

Antisense ubiquitin carboxyl-terminal hydrolase L1(UCHL1-AS1), a novel nuclear-enriched long noncoding RNA(LncRNA), is antisense to a well known coding RNA ubiquitin carboxy-terminal hydrolase L1 (UCHL1). It was reported that UCHL1-AS1 increased UCHL1 protein synthesis at a post-transcriptional level. UCHL1 can inhibit proliferation and accelerate apoptosis of human hepatocellular carcinoma(HCC) while the function of UCHL1-AS1 remains unclarified. In our previous study, we found that UCHL1-AS1 presented low level in HCC tissues and cell lines, and the level of UCHL1-AS1 was associated with portal vein tumor embolus. Based on these findings, our hypothesis is that UCHL1-AS1 may inhibit the proliferation, metastasis and accelerate apoptosis of HCC by targeting UCHL1. To verify this hypothesis, we design the study from molecule, cell, tissue and animal levels. QRT-PCR, in situ hybridization, Western blot, RNA interference will be conducted. The clinical significance of UCHL1-AS1 expression will be explored. The important contribution of UCHL1-AS1 to HCC biological function will be confirmed. Furthermore, the association between UCHL1-AS1 and UCHL1 and the underlying mechanism of UCHL1-AS1 in HCC will be investigated. Focusing in the insight of UCHL1-AS1, this study will reveal the mechanism of HCC and provide a new target for clinical strategy of HCC.