肝细胞核因子1α(HNF1α)系维持肝细胞分化和功能的重要转录因子。我们研究发现HNF1α可诱导肝癌细胞向肝细胞分化，显著抑制肝脏种植瘤生长。HNF1A-AS1基因为一功能尚不明确的长链非编码RNA，位于HNF1α基因上游6.5kb。我们前期发现HNF1α可上调肝癌细胞HNF1A-AS1的表达，过表达HNF1A-AS1可抑制肝癌细胞增殖、迁移和克隆形成，并促进HNF1α的表达，提示HNF1A-AS1与HNF1α二者之间存在相互调控并影响肝癌发生发展。本课题拟分析HNF1A-AS1表达与肝癌患者临床恶性表型和预后的关系，体内外实验观察HNF1A-AS1对肝癌细胞恶性生物学行为的影响及实验性肝癌的治疗效果，阐明HNF1A-AS1与HNF1α的相互调控机制，确定HNF1A-AS1的相互作用蛋白，明确HNF1A-AS1抑制肝癌的分子机制。研究成果将进一步揭示肝癌发生发展机制，为肝癌诊治提供新靶点。

Hepatocyte nuclear factor 1α (HNF1α) is one of the key transcription factors which plays a critical role in hepatocyte differentiation and liver function maintenance. Our previous studies showed that forced expression of HNF1α induced the differentiation of hepatocellular carcinoma (HCC) cells into hepatocytes and significantly inhibited the growth of the orthotopic HCC nodules in the liver. HNF1α antisense RNA 1 (HNF1A-AS1) is a long noncoding RNA located on the 6.5kb upstream of HNF1α gene, which function remains largely enigmatic. Our previous microarray analysis indicated that HNF1α induced the expression of HNF1A-AS1 in HCC cells. Overexpression of HNF1A-AS1 suppressed the proliferation, migration and colony formation of HCC cells in accompanied with the up-regulation of HNF1α. These data suggest a bidirectional regulation between HNF1A-AS and HNF1α which may affect HCC progression. Based on our previous findings, the present project aims to analyze the relationship between HNF1A-AS1 levels and the clinical malignant phenotypes as well as the prognosis of human HCC patients. In addition, we will evaluate the impact of HNF1A-AS1 on the malignant behaviors of HCC cells both in vitro and in vivo as well as its therapeutic efficacy on experimental HCC in mice. Moreover, the molecular mechanism of bidirectional regulation between HNF1A-AS1 and HNF1α will be clarified. Finally, the binding protein of HNF1A-AS1 and the signal pathway affected by HNF1A-AS1 will be identified to further elucidate the molecular mechanism by which HNF1A-AS1 inhibits the development and progression of HCC. This study will shed new light on the molecular mechanism of hepatocarcinogenesis and provide novel targets for the diagnosis and treatment of HCC.