Zeng Bing, Lin Zewei, Ye Huilin, Cheng Di, Zhang Guangtao, Zhou Jindu, Huang Zhifeng, Wang Meng, Cai Canfeng, Zeng Jun, Tang Chaoming, Liu Jikui
Department of Gastrointestinal Surgery, The Sixth Affiliated Hospital of Guangzhou Medical University, Qing Yuan People's Hospital, Guangdong, China.
Department of Hepatopancreatobiliary Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China.
Cell Physiol Biochem. 2018;46(3):1122-1133. doi: 10.1159/000488841. Epub 2018 Apr 13.
BACKGROUND/AIMS: Long noncoding RNAs (lncRNAs) are key regulators of cancer initiation and progression. In this study, we investigated the clinical value and functional role of LncRNA DQ786243 (LncDQ) in the pathogenesis of hepatocellular carcinoma (HCC).
To investigate the expression level of LncDQ in HCC, we performed quantitative real-time PCR using total RNA extracted from HCC tumor tissues and their matched non-neoplastic counterparts, as well as from the serum of HCC patients and healthy volunteers. The correlation of LncDQ expression with clinicopathologic features and prognosis was analyzed. The functional role of LncDQ in cell proliferation, migration, and invasion were evaluated by MTT cell viability, wound healing, and transwell assays in vitro and in vivo. RNA immunoprecipitation and chromatin immunoprecipitation assays were performed to analyze the potential mechanism of LncDQ in HCC cells.
LncDQ was upregulated in both HCC tissue samples and serum and was correlated with low survival rate and adverse clinical pathological characteristics. Multivariate analysis demonstrated that LncDQ expression was an independent prognostic factor for HCC. The area under the receiver operating characteristic curve was 0.804 with a sensitivity of 0.72 and a specificity of 0.8. Knockdown of LncDQ induced inhibition of cell proliferation, migration, and invasion in vitro and in vivo. Mechanistically, LncDQ regulated the epithelial-mesenchymal transition pathway by interacting with EZH2, to epigenetically repress the expression of E-cadherin in HCC cells.
Taken together, the results of our study indicate that LncDQ plays a critical role in HCC progression, and may serve as a potential diagnostic and prognostic biomarker for HCC.
背景/目的：长链非编码RNA（lncRNAs）是癌症发生和发展的关键调节因子。在本研究中，我们调查了LncRNA DQ786243（LncDQ）在肝细胞癌（HCC）发病机制中的临床价值和功能作用。
为研究LncDQ在HCC中的表达水平，我们使用从HCC肿瘤组织及其配对的非肿瘤组织以及HCC患者和健康志愿者血清中提取的总RNA进行定量实时PCR。分析LncDQ表达与临床病理特征及预后的相关性。通过MTT细胞活力、伤口愈合和体外及体内Transwell实验评估LncDQ在细胞增殖、迁移和侵袭中的功能作用。进行RNA免疫沉淀和染色质免疫沉淀实验以分析LncDQ在HCC细胞中的潜在机制。
LncDQ在HCC组织样本和血清中均上调，且与低生存率和不良临床病理特征相关。多因素分析表明，LncDQ表达是HCC的独立预后因素。受试者工作特征曲线下面积为0.804，敏感性为0.72，特异性为0.8。敲低LncDQ可在体外和体内诱导细胞增殖、迁移和侵袭的抑制。机制上，LncDQ通过与EZH2相互作用调节上皮-间质转化途径，从而表观遗传抑制HCC细胞中E-钙黏蛋白的表达。
综上所述，我们的研究结果表明LncDQ在HCC进展中起关键作用，可能作为HCC潜在的诊断和预后生物标志物。
