Long noncoding RNA PVT1 promotes hepatocellular carcinoma progression through regulating miR-214

Long noncoding RNA PVT1 promotes hepatocellular carcinoma progression through regulating miR-214
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DOI:
10.3233/cbm-170331
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发表时间:
2017-01-01
期刊:
影响因子:
3.1
通讯作者:
Wang, Zhengrong
Wang, Zhengrong
中科院分区:
医学3区
文献类型:
--
作者:
Gou, Xun;Zhao, Xiyan;Wang, Zhengrong

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背景:长链非编码rna (lncRNA)已被证实参与肝细胞癌(HCC)的进展。然而,PVT1在HCC中的潜在生物学功能尚不完全清楚。方法:采用qRT-PCR方法检测肝癌组织及邻近正常组织中PVT1和miR-214的表达。CCK8、细胞集落和transwell侵袭试验评估细胞增殖和侵袭能力。Western-blot法检测E-cadherin和Vimentin蛋白。QRT-PCR、RNA免疫沉淀(RIP)和染色质免疫沉淀(ChIP)检测显示PVT1调节miR-214的表达。结果:PVT1在HCC组织中表达升高,且PVT1的高表达与肿瘤大小、组织学分化程度、TNM分期有关。此外,我们发现PVT1促进了肝癌细胞的增殖和侵袭。RIP和ChIP实验表明,PVT1通过与zeste同源物增强子2 (EZH2)相互作用,显著抑制miR-214的表达。结论:因此,这些结果表明PVT1/EZH2/miR-214调控通路可能作为HCC治疗的新靶点。
BACKGROUND: Long noncoding RNAs (lncRNA) have been verified to be involved in hepatocellular carcinoma (HCC) progression. However, the potential biologic function of PVT1 in HCC is not still fully known.METHODS: PVT1 and miR-214 were detected by qRT-PCR assays in HCC tissues and adjacent normal tissues. CCK8, cell colony and transwell invasion assays were performed to evaluate cell proliferation and invasion abilities. Western-blot assay was performed to detect the protein of E-cadherin and Vimentin. QRT-PCR, RNA immunoprecipitation (RIP) and chromatin immunoprecipitation (ChIP) assays demonstrated PVT1 regulated miR-214 expression.RESULTS: The results showed that PVT1 was increased in HCC tissues and higher PVT1 expression was associated with tumor size, histological differentiation grade and advanced TNM stage. Furthermore, we revealed that PVT1 promoted cell proliferation and invasion in HCC. RIP and ChIP assays demonstrated that PVT1 significantly inhibited miR-214 expression by interacting with enhancer of zeste homolog 2 (EZH2).CONCLUSIONS: Thus, these results demonstrated that PVT1/EZH2/miR-214 regulatory pathway might serve as new target for HCC treatment.