Long non-coding RNA UBE2CP3 promotes tumor metastasis by inducing epithelial-mesenchymal transition in hepatocellular carcinoma.
Long non-coding RNA UBE2CP3 promotes tumor metastasis by inducing epithelial-mesenchymal transition in hepatocellular carcinoma.
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DOI：
10.18632/oncotarget.18524
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发表时间：
2017-09-12
期刊：
影响因子：
--
通讯作者：
Wang Q
中科院分区：
文献类型：
--
作者：
Cao SW;Huang JL;Chen J;Hu YW;Hu XM;Ren TY;Zheng SH;Lin JD;Tang J;Zheng L;Wang Q
肝细胞癌（HCC）是一种高度侵袭性的实体恶性肿瘤，预后不良。已发现长链非编码RNA（lncRNA）在各种癌症（包括HCC）中失调。然而，肝癌中涉及lncRNA的分子机制仍然很大程度上未知。在这项研究中，lncRNA差异表达肝癌和相应的非癌组织之间进行了鉴定，通过微阵列分析。鉴定了一个特异性差异表达的lncRNA UBE 2 CP 3（ubiquitin conjugating enzyme E2 C pseudogene 3）。LncRNA UBE 2CP 3在HCC样本中频繁上调，如通过定量实时聚合酶链反应（qRT-PCR）和原位杂交（ISH）实验所评估的。临床资料显示，高水平的lncRNA UBE 2CP 3与HCC患者的不良预后相关。功能研究表明，lncRNA UBE 2CP 3的过表达促进细胞在体外和体内的侵袭和迁移。其机制是，lncRNA UBE 2CP 3的表达增强，导致Snail 1和N-cadherin的表达增加，而E-cadherin的表达降低，从而促进上皮向间质转化（EMT）的过程，最终诱导细胞侵袭和迁移。此外，肝癌患者血清lncRNA UBE 2CP 3水平升高，手术后降低。提示lncRNA UBE 2CP 3促进肝癌的转移，血清lncRNA UBE 2CP 3可能成为肝癌诊断的一个新的生物标志物。
Hepatocellular carcinoma (HCC) is a highly aggressive, solid malignancy that has a poor prognosis. Long non-coding RNAs (lncRNAs) have been found to be dysregulated in various cancers, including HCC. However, the molecular mechanism involving lncRNAs in HCC remains largely unknown. In this study, lncRNAs differentially expressed between HCC and corresponding non-cancerous tissue were identified by microarray analysis. A specific differentially expressed lncRNA UBE2CP3 (ubiquitin conjugating enzyme E2 C pseudogene 3) was identified. LncRNA UBE2CP3 was frequently up-regulated in HCC samples as assessed by quantitative real-time polymerase chain reaction (qRT-PCR) and in situ hybridization (ISH) experiments. Clinical data showed that high levels of lncRNA UBE2CP3 were correlated with poor prognosis in HCC patients. Functional studies demonstrated that over-expression of lncRNA UBE2CP3 promoted cell invasion and migration in vitro and in vivo. Mechanistically, enhanced expression of lncRNA UBE2CP3 increased the expression of Snail1 and N-cadherin, but decreased the expression of E-cadherin, thus promoting the process of epithelial to mesenchymal transition (EMT) and finally inducing cell invasion and migration. Furthermore, serum levels of lncRNA UBE2CP3 were increased in HCC patients and decreased after surgery. Our results suggest that lncRNA UBE2CP3 promotes the metastasis of HCC and that serum lncRNA UBE2CP3 may be a new biomarker for the diagnosis of HCC.
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