Long non-coding RNA ANRIL is upregulated in hepatocellular carcinoma and regulates cell apoptosis by epigenetic silencing of KLF2.
Long non-coding RNA ANRIL is upregulated in hepatocellular carcinoma and regulates cell apoptosis by epigenetic silencing of KLF2.
复制标题
DOI：
10.1186/s13045-015-0146-0
复制
发表时间：
2015-05-14
影响因子：
28.5
通讯作者：
Shu YQ
中科院分区：
文献类型：
--
作者：
Huang MD;Chen WM;Qi FZ;Xia R;Sun M;Xu TP;Yin L;Zhang EB;De W;Shu YQ
肝细胞癌（HCC）是癌症相关死亡的主要原因之一，特别是在中国。其发展机制仍然知之甚少。越来越多的证据表明，长链非编码RNA（lncRNA）被发现在许多癌症，包括HCC中失调。ANRIL是一种主要与p14/ARF共簇的lncRNA，已报道在胃癌、食管鳞状细胞癌和肺癌中失调。然而，其临床意义和在HCC中的潜在作用仍然没有记录。本研究采用定量聚合酶链反应（qRT-PCR）检测了77例肝癌组织及相应正常肝组织中ANRIL的表达。ANRIL在HCC组织中表达上调，且ANRIL的高表达与肿瘤大小和巴塞罗那临床肝癌（BCLC）分期显著相关。此外，利用HCC细胞中的功能丧失实验，我们发现ANRIL表达的敲低可以在体外和体内损害细胞增殖和侵袭并诱导细胞凋亡。我们还发现ANRIL可以通过与PRC 2结合并将其募集到KLF 2启动子区域来表观遗传地抑制HCC细胞中的Kruppel样因子2（KLF 2）转录。我们还发现SP1可以调节ANRIL的表达。我们的研究结果表明，lncRNA ANRIL，作为一种生长调节剂，可作为一个新的生物标志物和治疗肝癌的目标。本文的在线版本（doi：10.1186/s13045-015-0146-0）包含补充材料，可供授权用户使用。
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death, especially in China. And the mechanism of its progression remains poorly understood. Growing evidence indicates that long non-coding RNAs (lncRNAs) are found to be dysregulated in many cancers, including HCC. ANRIL, a lncRNA co-clustered mainly with p14/ARF has been reported to be dysregulated in gastric cancer, esophageal squamous cell carcinoma, and lung cancer. However, its clinical significance and potential role in HCC are still not documented. In this study, expression of ANRIL was analyzed in 77 HCC tissues and matched normal tissues by using quantitative polymerase chain reaction (qRT-PCR). ANRIL expression was upregulated in HCC tissues, and the higher expression of ANRIL was significantly correlated with tumor size and Barcelona Clinic Liver Cancer (BCLC) stage. Moreover, taking advantage of loss-of-function experiments in HCC cells, we found that knockdown of ANRIL expression could impair cell proliferation and invasion and induce cell apoptosis both in vitro and in vivo. We also found that ANRIL could epigenetically repress Kruppel-like factor 2 (KLF2) transcription in HCC cells by binding with PRC2 and recruiting it to the KLF2 promoter region. We also found that SP1 could regulate the expression of ANRIL. Our results suggest that lncRNA ANRIL, as a growth regulator, may serve as a new biomarker and target for therapy in HCC. The online version of this article (doi:10.1186/s13045-015-0146-0) contains supplementary material, which is available to authorized users.
登录
查看更多内容
影响因子：
64.8
作者：
通讯作者：
--
BRAF激活的非编码RNA的下调与非小细胞肺癌的不良预后相关，并通过影响上皮间质转化促进转移
影响因子：
37.3
作者：
Sun M;Liu XH;Wang KM;Nie FQ;Kong R;Yang JS;Xia R;Xu TP;Jin FY;Liu ZJ;Chen JF;Zhang EB;De W;Wang ZX
通讯作者：
Wang ZX
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。
影响因子：
5.7
作者：
Nie, Feng-qi;Sun, Ming;Shu, Yong-qian
通讯作者：
Shu, Yong-qian
RNA在意外的地方：长的非编码RNA在不同的细胞环境中起作用。
DOI：
10.1038/nrm3679
发表时间：
2013-11
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
Geisler S;Coller J
通讯作者：
Coller J
影响因子：
12.3
作者：
Kaczynski J;Cook T;Urrutia R
通讯作者：
Urrutia R