Long Noncoding RNA AFAP1-AS1 Promoted Tumor Growth and Invasion in Cholangiocarcinoma
Long Noncoding RNA AFAP1-AS1 Promoted Tumor Growth and Invasion in Cholangiocarcinoma
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DOI：
10.1159/000477319
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发表时间：
2017-01-01
影响因子：
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通讯作者：
Zhai, Wenlong
中科院分区：
文献类型：
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作者：
Lu, Xu;Zhou, Chuang;Zhai, Wenlong
背景资料：长链非编码RNA（lncRNA）已被证明在广泛的病理生理过程中发挥重要作用，包括癌症进展。我们的前期研究表明AFAP 1-AS 1在肝细胞癌中表达上调，并作为癌基因发挥作用。然而，lncRNA AFAP 1-AS 1在肝内胆管癌（CCA）中的表达及其生物学功能尚不清楚。研究方法：检测56对人胆管癌组织及相应癌旁正常胆管组织中AFAP 1-AS 1的表达水平。采用卡方检验分析AFAP 1-AS 1与临床病理特征的相关性。采用CCK-8法、克隆形成实验、流式细胞术和transwell实验检测AFAP 1-AS 1对CCA细胞的作用。最后，为了确定AFAP 1-AS 1对体内肿瘤生长的影响，将AFAP 1-AS 1敲除的CCLP-1细胞皮下植入裸鼠以评估肿瘤生长。结果如下：在这项研究中，我们发现lncRNA AFAP 1-AS 1在CCA组织中增加，并且AFAP 1-AS 1高表达的患者的总生存期较短。siRNA介导的AFAP 1-AS 1基因敲低可显著抑制CCA细胞的增殖，同时下调C-myc和Cycling D1的表达。AFAP 1-AS 1沉默可抑制细胞迁移，其机制可能与抑制MMP-2和MMP-9的表达有关。此外，将AFAP 1-AS 1基因敲减的CCLP-1细胞注射到裸鼠体内，以研究AFAP 1-AS 1对体内成瘤的影响。结论：综上所述，我们的研究结果表明，AFAP 1-AS 1可能促进CCA的进展，并提供了一个新的潜在的治疗CCA的目标。(C)2017作者（s）由S. Karger AG，巴塞尔
Background: Long non-coding RNAs (lncRNAs) have been shown to play important roles in a wide range of pathophysiological processes, including cancer progression. Our previous study has shown that AFAP1-AS1 was upregulated and acted as an oncogene in hepatocellular carcinoma. However, the expression and biological functions of lncRNA AFAP1-AS1 in intrahepatic cholangiocarcinoma (CCA) remains largely unknown. Methods: The expression level of AFAP1-AS1 was measured in 56 pairs of human cholangiocarcinoma tumor tissues and corresponding adjacent normal bile duct tissues. The correlation between AFAP1-AS1 and the clinicopathological features were evaluated by chi-square test. The effects of AFAP1-AS1 on CCA cells were determined by CCK-8 assay, clone formation assay, flow cytometry and transwell assay. Finally, to determine the effect of AFAP1-AS1 on tumor growth in vivo, AFAP1-AS1 knockdowned CCLP-1 cells were subcutaneously into nude mice to evaluate tumor growth. Results: In this study, we found that lncRNA AFAP1-AS1 was increased in CCA tissues and patients with high AFAP1-AS1 expression had a shorter overall survival. SiRN-Amediated AFAP1-AS1 knockdown significantly decreased cell proliferation of the CCA cells, with downregulation of C-myc and Cycling D1 in vitro. Furthermore, AFAP1-AS1 silencing inhibited cell migration partly due to decrease the expression of MMP-2 and MMP-9. In addition, CCLP-1 cells with AFAP1-AS1 knockdown were injected into nude mice to investigate the effect of AFAP1-AS1 on the tumorigenesis in vivo. Conclusions: Taken together, our findings suggested that AFAP1-AS1 might promote the CCA progression and provided a novel potential therapeutic target for CCA. (C) 2017 The Author(s) Published by S. Karger AG, Basel