一种长链非编码RNA UCA1促进胶质瘤增殖并预示不良预后。

A long noncoding RNA UCA1 promotes proliferation and predicts poor prognosis in glioma.

作者信息

Zhao W, Sun C, Cui Z

机构信息

Department of Neurosurgery, The Affiliated 2ed Hospital of Nantong University, 6 Baby Lane North Road, Nantong, 226001, Jiangsu, China.

Department of Neurosurgery, Zhejiang Cancer Hospital, 38 Guangji Road, Hangzhou, 310022, Zhejiang, China.

出版信息

Clin Transl Oncol. 2017 Jun;19(6):735-741. doi: 10.1007/s12094-016-1597-7. Epub 2017 Jan 19.

Abstract

BACKGROUND

Acting as a proto-oncogene, long noncoding RNAs (lncRNAs) urothelial carcinoembryonic antigen 1 (UCA1) plays a key role in the occurrence and development of several human tumors. However, the expression and biological functions of UCA1 in glioma are less known. This study discussed the expression of UCA1 in glioma and its effect on the proliferation and cell cycle of glioma cells.

METHOD

LncRNA UCA1 expressions in 64 glioma samples (Grade I-II in 22 cases and Grade III-IV in 42 cases, according to WHO criteria) and 10 normal brain samples were detected using real-time fluorescence quantitative PCR. On this basis, the correlations of UCA1 to clinicopathological characteristics and prognosis of glioma were assessed. Then, using qPCR, the lncRNA UCA1 expressions in glioma cell lines and astrocytes were detected. UCA1-overexpressing glioma cell lines U87 and U251 were further detected after siRNA transfection of these two cell lines, and the impact on cell proliferation and cell cycle was assessed with CCK-8 (cell counting kit-8) assay and flow cytometry method (FCM), respectively. The expression of cyclin D1, a cell cycle-related protein, was detected using Western Blot.

RESULT

LncRNA UCA1 expression in the glioma samples was obviously higher as compared with the normal brain samples (P < 0.001), and the expression was correlated significantly with grading of the tumors (P < 0.05). However, lncRNA UCA1 expression was not correlated with age, gender, tumor size and KPS score (P > 0.05). After interference of UCA1 expression by siRNA transfection, the proliferation of both U251 and SHG-44 cells was inhibited (P < 0.05), with more cells arrested in G0/G1 (P < 0.05). Moreover, cyclin D1 expression was also downregulated considerably.

CONCLUSION

LncRNA UCA1 can promote the proliferation and cell cycle progression of glioma cells by upregulating cyclin D1 transcription. So UCA1 may serve as an independent prognostic indicator and a novel therapeutic target for glioma.

摘要

背景

长链非编码RNA(lncRNA)尿路上皮癌胚抗原1(UCA1)作为一种原癌基因,在多种人类肿瘤的发生和发展中起关键作用。然而,UCA1在胶质瘤中的表达及生物学功能尚鲜为人知。本研究探讨了UCA1在胶质瘤中的表达及其对胶质瘤细胞增殖和细胞周期的影响。

方法

采用实时荧光定量PCR检测64例胶质瘤样本(根据WHO标准,其中22例为I-II级,42例为III-IV级)和10例正常脑样本中lncRNA UCA1的表达。在此基础上,评估UCA1与胶质瘤临床病理特征及预后的相关性。然后,用qPCR检测胶质瘤细胞系和星形胶质细胞中lncRNA UCA1的表达。对U87和U251这两种UCA1过表达的胶质瘤细胞系进行siRNA转染后进一步检测,分别用CCK-8(细胞计数试剂盒-8)法和流式细胞术(FCM)评估对细胞增殖和细胞周期的影响。采用蛋白质免疫印迹法检测细胞周期相关蛋白细胞周期蛋白D1的表达。

结果

与正常脑样本相比,胶质瘤样本中lncRNA UCA1的表达明显更高(P<0.001),且该表达与肿瘤分级显著相关(P<0.05)。然而,lncRNA UCA1的表达与年龄、性别、肿瘤大小和KPS评分无关(P>0.05)。通过siRNA转染干扰UCA1表达后,U251和SHG-44细胞的增殖均受到抑制(P<0.05),更多细胞停滞在G0/G1期(P<0.05)。此外,细胞周期蛋白D1的表达也显著下调。

结论

lncRNA UCA1可通过上调细胞周期蛋白D1转录促进胶质瘤细胞的增殖和细胞周期进程。因此,UCA1可能作为胶质瘤的独立预后指标和新型治疗靶点。

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