LncRNA-CCAT1 Promotes Migration, Invasion, and EMT in Intrahepatic Cholangiocarcinoma Through Suppressing miR-152

LncRNA-CCAT1 Promotes Migration, Invasion, and EMT in Intrahepatic Cholangiocarcinoma Through Suppressing miR-152
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LncRNA-CCAT1 通过抑制 miR-152 促进肝内胆管癌的迁移、侵袭和 EMT

DOI:
10.1007/s10620-017-4759-8
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发表时间:
2017-09
影响因子:
3.1
通讯作者:
Zhou Wei
Zhou Wei
中科院分区:
医学3区
文献类型:
--
作者:
Zhang Shouhua;Xiao Juhua;Chai Yong;Du Yun Yan;Liu Zhiqiang;Huang Kai;Zhou Xin;Zhou Wei

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越来越多的证据表明lncRNA CCAT 1在许多癌症中上调并作为潜在的肿瘤促进剂发挥作用。然而,CCAT 1在肝内胆管癌(intrahepatic cholangiocarcinoma,ICC)中的生物学作用及其调控机制尚不清楚。应用统计学分析评估CCAT 1表达与临床参数的预后价值和相关性。用siRNA沉默ICC细胞中的CCAT 1。Transwell法检测ICC细胞的迁移和侵袭能力。上皮间质转化(EMT)相关蛋白的表达进行了评估,以发现是否EMT的过程是involved.ResultsWe发现,CCAT 1的表达升高,在ICC组织相比,相邻的正常组织。我们还发现CCAT 1的高表达与ICC患者的肿瘤进展密切相关。此外,我们的研究结果表明,CCAT 1的敲低显着抑制ICC细胞的迁移和侵袭。此外,CCAT 1沉默显著逆转ICC细胞的EMT表型。此外,生物信息学分析和荧光素酶报告基因分析显示,CCAT 1直接结合到miR-152,其已被报道在多种癌症中充当肿瘤抑制因子。结论CCAT 1作为一种致癌lncRNA在ICC中发挥作用,可作为ICC诊断和治疗的潜在靶点。
BackgroundIncreasing evidence has suggested that lncRNA CCAT1 is upregulated and functions as a potential tumor promoter in many cancers. However, the potential biological roles and regulatory mechanisms of CCAT1 in intrahepatic cholangiocarcinoma (ICC) remain unclear.MethodsWe used real-time PCR to measure CCAT1 expression in ICC tissues and the adjacent normal tissues. The statistical analyses were applied to evaluate the prognostic value and associations of CCAT1 expression with clinical parameters. The CCAT1 was silenced with siRNA in ICC cells. The migration and invasion of ICC cells were detected with Transwell assay. The expressions of epithelial–mesenchymal transition (EMT)-related proteins were evaluated to discover whether the process of EMT was involved.ResultsWe found that CCAT1 expression was elevated in ICC tissues compared to the adjacent normal tissues. We also found that high CCAT1 expression is closely correlated with tumor progression in ICC patients. Furthermore, our results show that knockdown of CCAT1 significantly suppressed the migration and invasion of ICC cells. Additionally, CCAT1 silencing remarkably reverses the EMT phenotype of ICC cells. Moreover, bioinformatics analysis and luciferase reporter assay revealed that CCAT1 directly bound to the miR-152, which has been reported to serve as a tumor suppressor in variety cancers. Further investigation demonstrated that CCAT1 led to the metastasis and EMT activation of ICC cells through inhibiting miR-152.ConclusionsOur results suggested that CCAT1 functions as an oncogenic lncRNA in ICC, which could serve as a potential diagnostic and therapeutic target for ICC patients.
LncRNA CCAT1 作为胆管癌不良预后生物标志物
DOI: --
发表时间: 2017
期刊: Eur Rev Med Pharmacol Sci
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