Wang Fuqiang, Yang Huili, Deng Zhigang, Su Yongjie, Fang QinLiang, Yin Zhenyu
Department of Hepatobiliary Surgery, Zhongshan Hospital of Xiamen University, Fujian Provincial Key Laboratory of Chronic Liver Disease and Hepatocellular Carcinoma, Xiamen, Fujian, China.
Cell Physiol Biochem. 2016;40(1-2):287-296. doi: 10.1159/000452545. Epub 2016 Nov 18.
Recent studies reveal that long non-coding RNAs (LncRNAs) play critical roles in the proliferation and migration of human cancer. Previous report has shown that LncRNA HOXA-AS2 was involved in carcinoma processes. However, the expression and biological function of HOXA-AS2 in hepatocellular carcinoma (HCC) are poorly understood.
Quantitative real-time PCR (qRT-PCR) was performed to detect the expression of HOXA-AS2 in HCC tissues and cell lines. The relation between lncRNA HOXA-AS2 expression and clinicopathological characteristics was assessed by chi-square test. The prognosis was analyzed using Kaplan-Meier method, and compared differences between the two groups by log-rank test. The biological function of HOXA-AS2 on HCC cells were determined both in vitro and in vivo.
In the present study, we found that HOXA-AS2 expression was increased in HCC tissues and adjacent normal tissues and high HOXA-AS2 expression was associated with bigger tumor size, advanced tumor stage, and shorter survival time. Knockdown of HOXA-AS2 significantly inhibited HCC cell proliferation and invasion and resulted in an increase of apoptosis. Furthermore, inhibition of HOXA-AS2 in HCC cells significantly repressed tumorigenicity in nude mice.
Our results indicated that the inhibition of HOXA-AS2 in HCC cells significantly inhibited cell proliferation in vitro and in vivo, which might provide a potential possibility for targeted therapy of HCC.
近期研究表明,长链非编码RNA(LncRNAs)在人类癌症的增殖和迁移中发挥关键作用。先前的报告显示,LncRNA HOXA-AS2参与了癌症进程。然而,HOXA-AS2在肝细胞癌(HCC)中的表达及生物学功能仍知之甚少。
采用定量实时聚合酶链反应(qRT-PCR)检测HOXA-AS2在肝癌组织和细胞系中的表达。通过卡方检验评估lncRNA HOXA-AS2表达与临床病理特征之间的关系。采用Kaplan-Meier法分析预后,并通过对数秩检验比较两组之间的差异。在体外和体内确定HOXA-AS2对肝癌细胞的生物学功能。
在本研究中,我们发现HOXA-AS2在肝癌组织和癌旁正常组织中表达增加,且HOXA-AS2高表达与肿瘤体积较大、肿瘤分期较晚及生存时间较短相关。敲低HOXA-AS2可显著抑制肝癌细胞增殖和侵袭,并导致凋亡增加。此外,抑制肝癌细胞中的HOXA-AS2可显著抑制裸鼠的致瘤性。
我们的结果表明,抑制肝癌细胞中的HOXA-AS可显著抑制其在体外和体内的细胞增殖,这可能为肝癌的靶向治疗提供潜在可能性。