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长链非编码RNA UBE2CP3通过诱导肝细胞癌上皮-间质转化促进肿瘤转移。

Long non-coding RNA UBE2CP3 promotes tumor metastasis by inducing epithelial-mesenchymal transition in hepatocellular carcinoma.

作者信息

Cao Shun-Wang, Huang Jin-Lan, Chen Jing, Hu Yan-Wei, Hu Xiu-Mei, Ren Ting-Yu, Zheng Shi-Hao, Lin Jin-Duan, Tang Jing, Zheng Lei, Wang Qian

机构信息

Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.

Department of Clinical Laboratory, First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China.

出版信息

Oncotarget. 2017 Jun 16;8(39):65370-65385. doi: 10.18632/oncotarget.18524. eCollection 2017 Sep 12.

Abstract

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 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 and . 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.

摘要

肝细胞癌(HCC)是一种侵袭性很强的实体恶性肿瘤,预后较差。人们发现长链非编码RNA(lncRNA)在包括HCC在内的各种癌症中表达失调。然而,lncRNA在HCC中的分子机制仍 largely未知。在本研究中,通过微阵列分析鉴定了HCC与相应癌旁组织之间差异表达的lncRNA。鉴定出一种特异性差异表达的lncRNA UBE2CP3(泛素结合酶E2C假基因3)。通过定量实时聚合酶链反应(qRT-PCR)和杂交(ISH)实验评估,lncRNA UBE2CP3在HCC样本中经常上调。临床数据显示,lncRNA UBE2CP3的高水平与HCC患者的不良预后相关。功能研究表明,lncRNA UBE2CP3的过表达促进细胞侵袭和迁移。机制上,lncRNA UBE2CP3表达增强增加了Snail1和N-钙黏蛋白的表达,但降低了E-钙黏蛋白的表达,从而促进上皮-间质转化(EMT)过程,最终诱导细胞侵袭和迁移。此外,HCC患者血清中lncRNA UBE2CP3水平升高,术后降低。我们的结果表明,lncRNA UBE2CP3促进HCC转移,血清lncRNA UBE2CP3可能是HCC诊断的一种新生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a281/5630337/7be0395dbad1/oncotarget-08-65370-g001.jpg

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