Wang Fuqiang, Xie Chengrong, Zhao Wenxing, Deng Zhigang, Yang Huili, Fang Qinliang
Department of Hepatobiliary Surgery, Zhongshan Hospital of Xiamen University, Fujian Provincial Key Laboratory of Chronic Liver Disease and Hepatocellular Carcinoma, No. 201-209 Hubin South Road, Xiamen, 361000, Fujian, China.
Medical College of Xiamen University, Fujian Provincial Key Laboratory of Chronic Liver Disease and Hepatocellular Carcinoma, Xiamen, 361000, Fujian, China.
Clin Exp Med. 2017 Feb;17(1):33-43. doi: 10.1007/s10238-015-0395-9. Epub 2015 Oct 3.
Recently, many studies show that long non-coding RNAs (lncRNAs) play important roles in cancer biology. Although its expression was reported dysregulated during tumorigenesis, the contributions of lncRNAs to hepatocellular carcinoma (HCC) are still largely unknown. In particular, the lncRNA CARLo-5 has a functional role in cell-cycle regulation in colon cancer, while the clinical significance and biological function of CARLo-5 in HCC remain unelucidated. In order to fill those study blanks, the expression level of CARLo-5 in human HCC specimens was tested, and its correlation with clinicopathologic features as well as the prognosis for patients with HCC was analyzed. Additionally, MTT, wound healing and transwell assays were employed to investigate the biological function of CARLo-5. The results showed that CARLo-5 levels were significantly overexpressed in HCC tissues compared to ANLT. Besides, high expression of CARLo-5 was associated with liver cirrhosis (P = 0.001), tumor number (P < 0.001), vascular invasion (P = 0.001), capsular formation (P = 0.014) and Edmondson-Steiner grade (P < 0.001), which proved that CARLo-5 was an independent risk factor for overall survival and disease-free survival. In addition, in highly metastatic HCC cell lines (HCCLM3 and MHCC97-L), CARLo-5 was up-regulated, but in lowly metastatic HCC cell lines (HepG2, SNU387), it showed down-regulated. Besides, by using gain and loss of function experiments in HCC cell lines (HCCLM3 and HepG2), the results showed that CARLo-5 overexpression significantly enhanced cell proliferation, migration and invasion in vitro. Our study also revealed that CARLo-5 was prominently up-regulated in HCC specimens and its high expression was associated with poor prognosis of HCC patients. Totally, those findings together indicate that CARLo-5 promotes proliferation and metastasis of HCC and potentially emerged as a novel therapeutic target.
最近，许多研究表明长链非编码RNA（lncRNAs）在癌症生物学中发挥着重要作用。尽管有报道称其表达在肿瘤发生过程中失调，但lncRNAs对肝细胞癌（HCC）的作用仍 largely未知。特别是，lncRNA CARLo-5在结肠癌的细胞周期调控中具有功能作用，而CARLo-5在HCC中的临床意义和生物学功能仍未阐明。为了填补这些研究空白，检测了CARLo-5在人HCC标本中的表达水平，并分析了其与临床病理特征以及HCC患者预后的相关性。此外，采用MTT、伤口愈合和transwell实验来研究CARLo-5的生物学功能。结果显示，与癌旁正常肝组织（ANLT）相比，CARLo-5水平在HCC组织中显著上调。此外，CARLo-5的高表达与肝硬化（P = 0.001）、肿瘤数量（P < 0.001）、血管侵犯（P = 0.001）、包膜形成（P = 0.014）和Edmondson-Steiner分级（P < 0.001）相关，这证明CARLo-5是总生存和无病生存的独立危险因素。此外，在高转移HCC细胞系（HCCLM3和MHCC97-L）中，CARLo-5上调，但在低转移HCC细胞系（HepG2、SNU387）中，它呈下调。此外，通过在HCC细胞系（HCCLM3和HepG2）中进行功能获得和丧失实验，结果显示CARLo-5过表达显著增强了体外细胞增殖、迁移和侵袭。我们的研究还表明，CARLo-5在HCC标本中显著上调，其高表达与HCC患者的不良预后相关。总之，这些发现共同表明CARLo-5促进HCC的增殖和转移，并可能成为一个新的治疗靶点。
