Li Tong-Huai, Zhang Jing-Jing, Liu Shao-Xiao, Chen Yan
Department of Gynaecology & Obstetrics Department of Imaging, People's Hospital of Lishui City, the Sixth Affiliated Hospital of Wenzhou Medical University, Lishui, China.
Medicine (Baltimore). 2018 May;97(19):e0575. doi: 10.1097/MD.0000000000010575.
The aim of this study was to evaluate the correlation of long non-coding RNAs (lncRNAs) taurine-upregulated gene 1 (TUG1) with clinicopathological characteristics as well as overall survival (OS) in epithelial ovarian cancer (EOC) patients, and investigate its function in EOC cells proliferation and apoptosis in vitro.LncRNA TUG1 expressions were detected in tumor tissues and paired adjacent tissues obtained from 96 EOC patients. Blank mimic, lncRNA TUG1 mimic, blank inhibitor, and lncRNA TUG1 inhibitor plasmids were transfected into SKOV3 cells. CKK-8, annexin V-FITC-propidium iodide, qPCR and western blot assays were performed to detect cells proliferation, cells apoptosis, RNA expression, and protein expression, respectively.LncRNA TUG1 expression was higher in tumor tissue compared to paired adjacent tissue (P < .001), and it was positively correlated with pathological grade (P = .022), tumor size (P = .011) and FIGO stage (P < .001). Kaplan-Meier curve showed that lncRNA TUG1 high expression was associated with worse OS (P = .003). Multivariate Cox analysis indicated that lncRNA TUG1 high expression (vs. low expression) (P = .035) was independently predictive factor for shorter OS. In vitro, cells proliferation was promoted after treatment with lncRNA TUG1 mimic and was suppressed after treatment with lncRNA TUG1 inhibitor. In addition, cells apoptosis rate was decreased in lncRNA TUG1 mimic group compared to NC1 mimic, and increased in lncRNA TUG1 inhibitor group compared to NC2 inhibitor.In conclusion, lncRNA TUG1 is positively correlated with advanced disease and poor prognosis, and it promotes cells proliferation and inhibits cells apoptosis in EOC cells.
本研究旨在评估长链非编码RNA(lncRNA)牛磺酸上调基因1(TUG1)与上皮性卵巢癌(EOC)患者临床病理特征及总生存期(OS)的相关性,并研究其在EOC细胞体外增殖和凋亡中的作用。检测了96例EOC患者肿瘤组织及配对的癌旁组织中lncRNA TUG1的表达。将空白模拟物、lncRNA TUG1模拟物、空白抑制剂和lncRNA TUG1抑制剂质粒转染至SKOV3细胞。分别采用CCK-8、膜联蛋白V-FITC-碘化丙啶、qPCR和蛋白质印迹法检测细胞增殖、细胞凋亡、RNA表达和蛋白质表达。与配对的癌旁组织相比,lncRNA TUG1在肿瘤组织中的表达更高(P<0.001),且与病理分级(P = 0.022)、肿瘤大小(P = 0.011)和国际妇产科联盟(FIGO)分期(P<0.001)呈正相关。Kaplan-Meier曲线显示,lncRNA TUG1高表达与较差的OS相关(P = 0.003)。多因素Cox分析表明,lncRNA TUG1高表达(与低表达相比)(P = 0.035)是OS缩短的独立预测因素。在体外,lncRNA TUG1模拟物处理后细胞增殖得到促进,lncRNA TUG1抑制剂处理后细胞增殖受到抑制。此外,与NC1模拟物组相比,lncRNA TUG1模拟物组细胞凋亡率降低,与NC2抑制剂组相比,lncRNA TUG1抑制剂组细胞凋亡率升高。总之,lncRNA TUG1与晚期疾病及不良预后呈正相关,且促进EOC细胞的增殖并抑制其凋亡。