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首页> 外文期刊>EBioMedicine >Long noncoding RNA PCAT6 functions as an oncogene by binding to EZH2 and suppressing LATS2 in non-small-cell lung cancer
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Long noncoding RNA PCAT6 functions as an oncogene by binding to EZH2 and suppressing LATS2 in non-small-cell lung cancer

机译：长非编码RNA PCAT6通过与EZH2结合并抑制非小细胞肺癌中的LATS2而成为癌基因

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Background NSCLC (non-small-cell lung cancer) is the leading cause of cancer-related mortality worldwide. Both epigenetic and genetic changes contribute to the initiation, development and metastasis of NSCLC. Recently, accumulating data have begun to support the notion that long noncoding RNAs (lncRNAs) function as new crucial regulators of diverse biological processes, including proliferation, apoptosis and metastasis, and play crucial roles in tumorigenesis. Nevertheless, further study is warranted to comprehensively determine lncRNAs' functions and potential mechanism. Methods In this study, we performed a comprehensive analysis of the lncRNA expression profile of NSCLC using data from TCGA and Gene Expression Omnibus (GEO). PCAT6 expression level in a cohort of 60 pairs of NSCLC tissues using quantitative real-time PCR (qRT-PCR). Additionally, Loss-of-function assays and gain-of-function assays were used to assess the role of PCAT6 in promoting NSCLC progression. Tumor formation assay in a nude mouse model was performed to verity the role of PCAT6 in NSCLC in vivo. Meanwhile, RIP, ChIP, resue experiment and western blot assays were used to highlights the potential molecular mechanism of PCAT6 in NSCLC. Findings We identified that an oncogene, PCAT6, was upregulated in NSCLC, and this upregulation was verified in a cohort of 60 pairs of NSCLC tissues. Additionally, the expression level of PCAT6 was correlated with tumor size ( P =?.036), lymph node metastasis ( P ?=?.029) and TNM stage ( P ?=?.038). Loss-of-function and gain-of-function assays were used to assess the role of PCAT6 in promoting NSCLC progression. The results revealed that PCAT6 knockdown mitigated NSCLC cell growth by inducing G1-phase cell cycle arrest and apoptosis in vitro and in vivo. Whereas, PCAT6 overexpression could promoted tumor cell growth. Meanwhile, PCAT6 additionally promoted NSCLC cell migration and invasion. Furthermore, mechanistic investigation demonstrated that the oncogenic activity of PCAT6 is partially attributable to its repression of LATS2 via association with the epigenetic repressor EZH2 (Enhancer of zeste homolog 2). Overall, our study highlights the essential role of PCAT6 in NSCLC, suggesting that PCAT6 might be a potent therapeutic target for patients with NSCLC.
机译：背景技术NSCLC（非小细胞肺癌）是全球癌症相关死亡率的主要原因。表观遗传和遗传变化均有助于NSCLC的发生，发展和转移。最近，越来越多的数据开始支持长非编码RNA（lncRNA）作为多种生物过程（包括增殖，凋亡和转移）的新关键调节因子，并在肿瘤发生中起关键作用的观点。尽管如此，仍需要进一步研究以全面确定lncRNA的功能和潜在机制。方法在这项研究中，我们使用TCGA和Gene Expression Omnibus（GEO）的数据对NSCLC的lncRNA表达谱进行了全面分析。使用实时定量PCR（qRT-PCR）在60对非小细胞肺癌组织中的PCAT6表达水平。另外，功能丧失测定法和功能获得测定法用于评估PCAT6在促进NSCLC进展中的作用。在裸鼠模型中进行肿瘤形成测定以证实PCAT6在体内NSCLC中的作用。同时，通过RIP，ChIP，resue实验和western blot分析来强调PCAT6在NSCLC中的潜在分子机制。结果我们发现癌基因PCAT6在NSCLC中被上调，并且在60对NSCLC组织中证实了这种上调。另外，PCAT6的表达水平与肿瘤的大小（P ＝ 0.01.036），淋巴结转移（P ＝ 0.029）和TNM分期（P ＝ 0.038）相关。功能丧失和功能获得分析用于评估PCAT6在促进NSCLC进展中的作用。结果表明，PCAT6敲低通过在体内外诱导G1期细胞周期停滞和凋亡来减轻NSCLC细胞的生长。而PCAT6的过度表达可能促进肿瘤细胞的生长。同时，PCAT6还促进了NSCLC细胞的迁移和侵袭。此外，机理研究表明，PCAT6的致癌活性部分归因于其通过与表观遗传抑制因子EZH2（zeste同源物2的增强子）的结合而抑制了LATS2。总体而言，我们的研究突出了PCAT6在NSCLC中的重要作用，表明PCAT6可能是NSCLC患者的有效治疗靶标。

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