Department of Oncology, Sichuan Cancer Hospital and Institute. No.55, the forth section of South Renmin Road, Wuhou District, Chengdu, Sichuan, China.
Cancer Center, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan, China.
J Cell Physiol. 2018 Jun;233(6):4726-4734. doi: 10.1002/jcp.26257. Epub 2017 Dec 26.
Hepatocellular carcinoma (HCC) has been identified as one of the leading causes of cancer-related death worldwide. Recently, long non-coding RNAs (lncRNAs) attract much attention of researchers, and they are demonstrated to be dysregulated in a variety of cancers, including HCC. LncRNA gastric carcinoma high expressed transcript 1 lncRNA GHET1 is found to be dysregulated in gastric cancer (GC). However, its clinical value and potential biological function in HCC remains unclear. In this study, the expression level of GHET1 was analyzed in 72 HCC tissues and matched normal tissues by using Quantitative RT-PCR (qRT-PCR). GHET1 expression was significantly up-regulated in HCC tissues and the higher level of GHET1 was related to vascular invasion, cirrhosis, tumor size, edmindson grade, and poor prognosis. Moreover, knockdown of GHET1 inhibited cell proliferation of HCC, and also caused cell cycle arrest and induced apoptosis in HCC cell lines. We also found that GHET1 could epigenetically repress transcription of Kruppel-like factor 2 (KLF2) in HCC cells by recruiting PRC2 into KLF2 promoter region. Our results indicated that lncRNA GHET1, as a growth regulator, might serve as a novel prognostic biomarker and therapy target for HCC.
肝细胞癌（HCC）已被确定为全球癌症相关死亡的主要原因之一。最近，长非编码 RNA（lncRNA）引起了研究人员的极大关注，并且已经证明它们在多种癌症中失调，包括 HCC。lncRNA 胃癌高表达转录本 1 lncRNA GHET1 在胃癌（GC）中被发现失调。然而，其在 HCC 中的临床价值和潜在生物学功能尚不清楚。在这项研究中，通过定量 RT-PCR（qRT-PCR）分析了 72 例 HCC 组织和配对的正常组织中的 GHET1 表达水平。GHET1 在 HCC 组织中表达明显上调，并且 GHET1 水平越高与血管侵犯、肝硬化、肿瘤大小、edmindson 分级和预后不良相关。此外，敲低 GHET1 抑制 HCC 细胞的增殖，并且还导致 HCC 细胞系中的细胞周期停滞和诱导细胞凋亡。我们还发现，GHET1 通过募集 PRC2 到 KLF2 启动子区域，在 HCC 细胞中可以表观遗传抑制 Kruppel 样因子 2（KLF2）的转录。我们的结果表明，lncRNA GHET1 作为一种生长调节剂，可能成为 HCC 的新型预后标志物和治疗靶标。
