A Novel Long Non-Coding RNA, SOX21-AS1, Indicates a Poor Prognosis and Promotes Lung Adenocarcinoma Proliferation

A Novel Long Non-Coding RNA, SOX21-AS1, Indicates a Poor Prognosis and Promotes Lung Adenocarcinoma Proliferation
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DOI:
10.1159/000479543
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发表时间:
2017-01-01
影响因子:
--
通讯作者:
Guo, Renhua
Guo, Renhua
中科院分区:
医学1区
文献类型:
--
作者:
Lu, Xiyi;Huang, Chenjun;Guo, Renhua

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背景:近年来,长链非编码RNA(longnoncodingRNA,lncRNA)被发现是一类新的肿瘤生物学过程调控因子。尽管lncRNA在许多癌症类型中失调,但关于lncRNA在肺腺癌(LUAD)中的表达谱和潜在功能的数据有限。本研究旨在探讨lncRNA SOX 21反义RNA 1(SOX 21-AS 1)在LUAD中的表达及其生物学作用。研究方法:采用定量逆转录聚合酶链反应(qRT-PCR)检测68对LUAD组织及相应非肿瘤组织中SOX 21-AS 1的表达水平。通过MTT、集落形成、EdU测定、流式细胞术分析和体内肿瘤形成测定来评估SOX 21-AS 1对增殖的影响。采用实时荧光定量PCR、免疫印迹和免疫组化方法检测p57基因mRNA和蛋白表达。结果:SOX 21-AS 1的高表达水平与肿瘤的大小和TNM分期呈正相关。多因素分析表明,SOX 21-AS 1表达可作为LUAD总生存期的独立预后因素。此外,SOX 21-AS 1基因的敲低在体内外均显著抑制LUAD细胞的增殖,并诱导细胞周期阻滞和细胞凋亡。重要的是,通过qRT-PCR和western blot分析,我们发现抑制SOX 21-AS 1显著诱导p57表达。结论:总的来说,我们的研究表明,SOX 21-AS 1参与了LUAD的发展和进展,SOX 21-AS 1可能是一个潜在的诊断因子,也可能是LUAD患者新疗法的靶点。(C)2017作者(s)由S. Karger AG,巴塞尔
Background: In recent years, long non-coding RNAs (lncRNAs) have been shown to be a novel class of regulators of cancer biological processes. Although lncRNAs are dysregulated in numerous cancer types, limited data are available on the expression profiles and potential functions of lncRNAs in lung adenocarcinoma (LUAD). This study evaluated the expression and biological roles of lncRNA SOX21 antisense RNA 1 (SOX21-AS1) in LUAD. Methods: Quantitative reverse transcription PCR (qRT-PCR) was performed to detect the expression levels of SOX21-AS1 in 68 pairs of LUAD tissues and corresponding non-tumor tissues. The effect of SOX21-AS1 on proliferation was evaluated by MTT, colony formation, EdU assays, flow-cytometric analysis and in vivo tumor formation assays. Real-time PCR, western-blot and immunohistochemistry were used to evaluate the mRNA and protein expression of p57. Results: Higher expression levels of SOX21-AS1 positively correlated with tumor size and advanced tumor-node-metastasis (TNM) stage. Multivariate analyses indicated that SOX21-AS1 expression could serve as an independent prognostic factor for overall survival of LUAD. Furthermore, knockdown of SOX21-AS1 significantly inhibited LUAD cell proliferation both in vitro and in vivo and induced cell cycle phase arrest and cell apoptosis. Importantly, through qRT-PCR and western blot analysis, we found that inhibition of SOX21-AS1 remarkably induced p57 expression. Conclusions: Collectively, our study demonstrates that SOX21-AS1 is involved in the development and progression of LUAD and that SOX21-AS1 may be a potential diagnostic factor as well as a target for new therapies for patients with LUAD. (C) 2017 The Author(s) Published by S. Karger AG, Basel