A long non-coding RNA HOTTIP expression is associated with disease progression and predicts outcome in small cell lung cancer patients.
A long non-coding RNA HOTTIP expression is associated with disease progression and predicts outcome in small cell lung cancer patients.
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长非编码 RNA HOTTIP 表达与疾病进展相关并预测小细胞肺癌患者的结果
DOI：
10.1186/s12943-017-0729-1
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发表时间：
2017-10-17
期刊：
影响因子：
37.3
通讯作者：
Guo L
中科院分区：
文献类型：
--
作者：
Sun Y;Zhou Y;Bai Y;Wang Q;Bao J;Luo Y;Guo Y;Guo L
背景尽管小细胞肺癌（SCLC）的治疗取得了进展，但对肿瘤的生物学仍然知之甚少。最近，我们在全球范围内研究了lncRNA在SCLC中的作用，特别关注海绵调控网络。本文报道了HOTTIP基因在小细胞肺癌中特异性扩增，并与小细胞肺癌的增殖和预后密切相关。通过CCK 8测定、集落形成测定、流式细胞术分析和裸鼠体内SCLC异种移植模型，通过HOTTIP功能丧失和获得效应，证明HOTTIP在SCLC细胞增殖中的作用。蛋白质印迹分析用于在蛋白质水平上评估细胞系中的基因表达。通过RNA pull-down、质谱分析和RNA结合蛋白免疫沉淀（RIP）等方法研究HOTTIP参与SCLC进展的分子机制。结果发现HOTTIP在SCLC组织中过表达，且其表达与SCLC患者的临床分期和较短的生存期相关。HOTTIP基因敲低可抑制细胞增殖、影响细胞周期、抑制肿瘤生长，而HOTTIP基因过表达可增强体内外细胞增殖和细胞周期。结论HOTTIP通过“HOTTIP/miR-574 - 5 p/EZH 1”的ceRNA网络参与SCLC的发生发展。我们的研究结果不仅阐明了HOTTIP如何在SCLC发病机制中赋予致癌功能，而且还强调了一种新的基因表达在疾病中的标志。
BackgroundDespite progress in treatment of small cell lung cancer (SCLC), the biology of the tumor still remains poorly understood. Recently, we globally investigated the contributions of lncRNA in SCLC with a special focus on sponge regulatory network. Here we report lncRNA HOTTIP, which is specifically amplified in SCLC, is associated with SCLC proliferation and poor prognosis of patients.MethodsRT-qPCR was used to investigate the expression of HOTTIP in SCLC tissues and cell lines. The role of HOTTIP in SCLC cell proliferation was demonstrated by CCK8 assay, colony formation assay, flow cytometry analysis and in vivo SCLC xenograft model in nude mice through HOTTIP loss- and gain-of-function effects. Western blot assay was used to evaluate gene expression in cell lines at protein level. RNA pull-down, Mass spectrometry and RNA binding protein immunoprecipitation (RIP) were performed to confirm the molecular mechanism of HOTTIP involved in SCLC progression.ResultsWe found that HOTTIP was overexpressed in SCLC tissues, and its expression was correlated with the clinical stage and the shorter survival time of SCLC patients. Moreover, HOTTIP knockdown could impair cell proliferation, affect the cell cycle and inhibit tumor growth of mice, while HOTTIP overexpression might enhance cell proliferation and cell cycle in vitro and in vivo. Mechanistic investigations showed that HOTTIP functions as an oncogene in SCLC progression by sponging miR-574-5p and affecting the expression of polycomb group protein EZH1.ConclusionsOverall, we identified that HOTTIP was involved in SCLC tumorigenesis through the ceRNA network “HOTTIP/miR-574-5p/EZH1”. Our findings not only illuminate how HOTTIP confers an oncogenic function in SCLC pathogenesis, but also underscore a novel gene expression governing hallmarks in the disease.
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影响因子：
64.8
作者：
通讯作者：
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影响因子：
37.3
作者：
Huang MD;Chen WM;Qi FZ;Sun M;Xu TP;Ma P;Shu YQ
通讯作者：
Shu YQ
影响因子：
64.8
作者：
通讯作者：
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非编码 RNA：细胞中的多任务分子。
影响因子：
5.6
作者：
Gomes AQ;Nolasco S;Soares H
通讯作者：
Soares H
lncRNA H19 在结直肠癌中充当 miRNA 海绵，促进上皮细胞向间质细胞的转变。
影响因子：
--
作者：
Liang WC;Fu WM;Wong CW;Wang Y;Wang WM;Hu GX;Zhang L;Xiao LJ;Wan DC;Zhang JF;Waye MM
通讯作者：
Waye MM