Long Noncoding RNA ANRIL Promotes Non-Small Cell Lung Cancer Cell Proliferation and Inhibits Apoptosis by Silencing KLF2 and P21 Expression
Long Noncoding RNA ANRIL Promotes Non-Small Cell Lung Cancer Cell Proliferation and Inhibits Apoptosis by Silencing KLF2 and P21 Expression
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长非编码 RNA ANRIL 通过沉默 KLF2 和 P21 表达促进非小细胞肺癌细胞增殖并抑制细胞凋亡。
DOI：
10.1158/1535-7163.mct-14-0492
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发表时间：
2015-01-01
影响因子：
5.7
通讯作者：
Shu, Yong-qian
中科院分区：
文献类型：
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作者：
Nie, Feng-qi;Sun, Ming;Shu, Yong-qian
最近的证据表明，长非编码RNA(LncRNA)是癌症生物学的关键调节因子，有助于肿瘤细胞的基本功能，如细胞增殖、凋亡和转移。在非小细胞肺癌(NSCLC)中，一些lncRNAs的表达受到错误调控，已被提名为NSCLC肿瘤发生中的关键因子。LncRNA ANRIL首先被发现与p15(INK4B)的PRC2募集和沉默有关，它的表达是由ATM-E2F1信号通路诱导的。我们先前的研究表明，ANRIL在胃癌中显著上调，并通过沉默miR99a和miR449a转录而促进细胞增殖和抑制细胞凋亡。然而，它的临床意义和在非小细胞肺癌中的潜在作用仍然没有文献记载。在本研究中，我们报道了ANRIL在非小细胞肺癌组织中的表达增加，其表达水平与肿瘤转移分期和肿瘤大小显著相关。此外，ANRIL高表达的患者预后相对较差。此外，利用非小细胞肺癌细胞的功能丧失实验，我们发现在体外和体内，下调ANRIL的表达都可以损害细胞的增殖和诱导细胞的凋亡。此外，我们还发现，ANRIL不能抑制PC9细胞中p15的表达，而是通过沉默KLF2和p21转录来实现的。因此，我们最终证明了lncRNA ANRIL通过将其表达与NSCLC患者的生存联系起来而在NSCLC的发展中发挥关键作用，为研究lncRNA驱动的肿瘤发生的功能提供了新的见解。(C)2014年AACR。
Recent evidence highlights long noncoding RNAs (lncRNA) as crucial regulators of cancer biology that contribute to essential cancer cell functions such as cell proliferation, apoptosis, and metastasis. In non-small cell lung cancer (NSCLC), several lncRNAs' expressions are misregulated and have been nominated as critical actors in NSCLC tumorigenesis. LncRNA ANRIL was first found to be required for the PRC2 recruitment to and silencing of p15(INK4B), the expression of which is induced by the ATM-E2F1 signaling pathway. Our previous study showed that ANRIL was significantly upregulated in gastric cancer, and it could promote cell proliferation and inhibit cell apoptosis by silencing of miR99a and miR449a transcription. However, its clinical significance and potential role in NSCLC is still not documented. In this study, we reported that ANRIL expression was increased in NSCLC tissues, and its expression level was significantly correlated with tumor-node-metastasis stages and tumor size. Moreover, patients with high levels of ANRIL expression had a relatively poor prognosis. In addition, taking advantage of loss-of-function experiments in NSCLC cells, we found that knockdown of ANRIL expression could impair cell proliferation and induce cell apoptosis both in vitro and vivo. Furthermore, we uncover that ANRIL could not repress p15 expression in PC9 cells, but through silencing of KLF2 and P21 transcription. Thus, we conclusively demonstrate that lncRNA ANRIL plays a key role in NSCLC development by associating its expression with survival in patients with NSCLC, providing novel insights on the function of lncRNA-driven tumorigenesis. (C) 2014 AACR.