Over-expressed long noncoding RNA HOXA11-AS promotes cell cycle progression and metastasis in gastric cancer.
Over-expressed long noncoding RNA HOXA11-AS promotes cell cycle progression and metastasis in gastric cancer.
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过表达长非编码RNA HOXA11-AS促进胃癌细胞周期进展和转移
DOI：
10.1186/s12943-017-0651-6
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发表时间：
2017-04-26
期刊：
影响因子：
37.3
通讯作者：
Sun M
中科院分区：
文献类型：
--
作者：
Liu Z;Chen Z;Fan R;Jiang B;Chen X;Chen Q;Nie F;Lu K;Sun M
长链非编码RNA（lncRNA）已成为包括胃癌（GC）在内的多种人类癌症的关键调节因子。然而，这些分子在GC中的功能和机制尚未完全了解。在我们以前的研究中，我们发现GC相关的lncRNA HOXA 11-AS在GC组织中显著上调。过表达HOXA 11-AS通过支架化染色质修饰因子PRC 2、LSD 1和DNMT 1促进胃癌细胞增殖和侵袭。实时荧光定量PCR（qPCR）检测胃癌细胞HOXA 11-AS的表达水平。将HOXA 11-AS siRNA和过表达载体转染胃癌细胞，下调或上调HOXA 11-AS的表达。通过体外和体内实验研究HOXA 11-AS在胃癌细胞周期、侵袭和转移中的作用。RIP和ChIP测定用于确定HOXA 11-AS对潜在靶标的调节机制。我们发现HOXA 11-AS基因的敲除可诱导胃癌细胞G 0/G1期阻滞，并抑制胃癌细胞的迁移、侵袭和转移。HOXA 11-AS与WDR 5相互作用，促进β-catenin的转录;与EZH 2相互作用，抑制P21的转录;与STAU 1相互作用，诱导KLF 2的mRNA降解。这些结果表明HOXA 11-AS不仅可以促进胃癌细胞的体外迁移和侵袭，而且可以促进胃癌细胞的体内转移，至少部分是通过调节β-catenin和KLF 2来实现的。本文的在线版本（doi：10.1186/s12943-017-0651-6）包含补充材料，可供授权用户使用。
Long noncoding RNAs (lncRNAs) have emerged as critical regulators in a variety of human cancers, including gastric cancer (GC). However, the function and mechanisms responsible for these molecules in GC are not fully understood. In our previous study, we found that GC associated lncRNA HOXA11-AS is significantly upregulated in GC tissues. Over-expressed HOXA11-AS promotes GC cells proliferation and invasion through scaffolding the chromatin modification factors PRC2, LSD1 and DNMT1. HOXA11-AS expression levels in GC cells was detected by quantitative real-time PCR (qPCR). HOXA11-AS siRNAs and overexpression vector were transfected into GC cells to down-regulate or up-regulate HOXA11-AS expression. In vitro and in vivo assays were performed to investigate the functional role of HOXA11-AS in GC cells cell cycle progression, invasion and metastasis. RIP and ChIP assays were used to determine the mechanism of HOXA11-AS’s regulation of underlying targets. We found that knockdown of HOXA11-AS induced GC cells G0/G1 phase arrest and suppressed GC cells migration, invasion and metastasis in vivo. Moreover, mechanistic investigation showed that HOXA11-AS could interact with WDR5 and promote β-catenin transcription, bind with EZH2 and repress P21 transcription, and induce KLF2 mRNA degradation via interacting with STAU1. Taken together, these findings show that HOXA11-AS not only could promote GC cells migration and invasion in vitro, but also promotes GC cells metastasis in vivo, at least in part, by regulating β-catenin and KLF2. The online version of this article (doi:10.1186/s12943-017-0651-6) contains supplementary material, which is available to authorized users.