Wang Cong, Mou Lin, Chai Hai-Xia, Wang Feng, Yin Yun-Zhi, Zhang Xiao-Yu
Department of Hepatopancreatobiliary Surgery, Affiliated Hospital of Qinghai University, Xining, 810001, China.
Department of Ophthalmology, Affiliated Traditional Chinese Medicine Hospital Southwest Medical University, 182 Chunhui Road,Longmatan District,Luzhou,646000,China.
Biomed Pharmacother. 2017 May;89:926-932. doi: 10.1016/j.biopha.2017.01.031. Epub 2017 Mar 8.
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Recent evidences have demonstrated that long non-coding RNAs (lncRNAs) act as key regulators of tumor development and progression including HCC. In the study, we showed that the expression level of HNF1A-AS1 was up-regulated in HCC cell lines. Furthermore, CCK-8 cell proliferation assays and cell cycle analysis showed that HNF1A-AS1 over-expression facilitated HCC cell proliferation by promoting the cell proliferation and S-phase progression, whereas HNF1A-AS1 knockdown had the opposite effect. Western-blotting analysis revealed that knockdown of HNF1A-AS1 inhibited the cycle-relative protein cyclin-D1 and PCNA expression in HCC cells. Mechanism, RNA immunoprecipitation (RIP) and Chromatin immunoprecipitation (ChIP) assays showed that by interacting with enhancer of zeste homolog 2 (EZH2), HNF1A-AS1 promoted HCC cell proliferation by repressing the NKD1 and p21 expression. These results suggested that HNF1A-AS1 may contribute to HCC progression, which may be an effective therapeutic target for patients.
肝细胞癌（HCC）是全球最常见的癌症之一。最近的证据表明，长链非编码RNA（lncRNAs）是包括HCC在内的肿瘤发生发展的关键调节因子。在本研究中，我们发现HNF1A-AS1在HCC细胞系中的表达水平上调。此外，CCK-8细胞增殖试验和细胞周期分析表明，HNF1A-AS1过表达通过促进细胞增殖和S期进程促进HCC细胞增殖，而HNF1A-AS1敲低则产生相反的效果。蛋白质免疫印迹分析显示，敲低HNF1A-AS1可抑制HCC细胞中与细胞周期相关的蛋白细胞周期蛋白D1和增殖细胞核抗原（PCNA）的表达。机制方面，RNA免疫沉淀（RIP）和染色质免疫沉淀（ChIP）试验表明，HNF1A-AS1通过与zeste同源物2（EZH2）增强子相互作用，抑制NKD1和p21的表达，从而促进HCC细胞增殖。这些结果提示HNF1A-AS1可能促进HCC进展，这可能是患者的一个有效治疗靶点。
