Long non-coding RNA LUCAT1 is associated with poor prognosis in human non-small lung cancer and regulates cell proliferation via epigenetically repressing p21 and p57 expression.
Long non-coding RNA LUCAT1 is associated with poor prognosis in human non-small lung cancer and regulates cell proliferation via epigenetically repressing p21 and p57 expression.
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DOI：
10.18632/oncotarget.16044
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发表时间：
2017-04-25
期刊：
影响因子：
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通讯作者：
Guo RH
中科院分区：
文献类型：
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作者：
Sun Y;Jin SD;Zhu Q;Han L;Feng J;Lu XY;Wang W;Wang F;Guo RH
近年来，长链非编码rna （lncRNAs）被认为在细胞增殖、侵袭和转移等过程中发挥着关键作用。这些lncrna已被证明在致瘤过程中异常表达。然而，LUCAT1在非小细胞肺癌（NSCLC）中的作用和临床相关性尚不清楚。在本研究中，我们发现LUCAT1在NSCLC组织中的表达较非肿瘤组织明显上调，且其表达与肿瘤大小、肿瘤淋巴结转移（TNM）分期和总生存期（OS）相关。进一步的实验表明，LUCAT1敲低可以抑制体外和体内细胞的增殖。机制研究表明LUCAT1在G0/G1逮捕中起关键作用。我们进一步证明了LUCAT1与多梳抑制复合物（PRC2）相关，并且这种关联是p21和p57的表观遗传抑制所必需的，从而有助于调节NSCLC细胞周期和增殖。综上所述，我们的研究结果表明，LUCAT1可以调节非小细胞肺癌的肿瘤发生，是非小细胞肺癌预后不良的生物标志物。
Recently, long non-coding RNAs (lncRNAs) have been recognized as playing key roles in regulating cellular processes, such as proliferation, invasion, and metastasis. These lncRNAs have been shown to be abnormally expressed in tumorigenic processes. However, the role and clinical relevance of LUCAT1 in non-small-cell lung cancer (NSCLC) remain unclear. In this study, we found that the expression of LUCAT1 was significantly up-regulated in NSCLC tissues compared to non-tumor tissues, and its expression was associated with tumor size, tumor–node–metastasis (TNM) stage and overall survival (OS). Further experiments showed that LUCAT1 knockdown inhibited cell proliferation both in vitro and in vivo. Mechanistic investigations showed that LUCAT1 plays a key role in G0/G1 arrest. We further demonstrated that LUCAT1 was associated with polycomb repressor complexes (PRC2) and that this association was required for epigenetically repression of p21 and p57, thus contributing to the regulation of NSCLC cell cycle and proliferation. In summary, our results show that LUCAT1 could regulate tumorigenesis of NSCLC and be biomarker for poor prognosis in NSCLC.