lncRNA FLVCR1-AS1 regulates cell proliferation, migration and invasion by sponging miR-485-5p in human cholangiocarcinoma
lncRNA FLVCR1-AS1 regulates cell proliferation, migration and invasion by sponging miR-485-5p in human cholangiocarcinoma
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DOI：
10.3892/ol.2019.10577
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发表时间：
2019-09-01
期刊：
影响因子：
2.9
通讯作者：
Zhao, Bin
中科院分区：
文献类型：
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作者：
Bao, Wenqing;Cao, Feng;Zhao, Bin
长链非编码RNA（lncRNA）FLVCR 1反义RNA 1（FLVCR 1-AS 1）在许多类型的癌症中起关键作用;然而，据我们所知，FLVCR 1-AS 1在胆管癌（CCA）中的生物学效应仍不清楚。本研究旨在阐明FLVCR 1-AS 1在人CCA细胞生长、迁移和侵袭中的作用及其机制。采用逆转录-定量聚合酶链反应（RT-PCR）检测FLVCR 1-AS 1在CCA肿瘤组织、癌旁正常组织、CCA细胞系和胆管细胞系中的表达水平。FLVCR 1-AS 1在CCA肿瘤组织和CCA细胞系HuCCT 1和CCLP 1中的表达水平显著高于正常对照。将靶向FLVCR 1-AS 1的短发夹RNA（shFLVCR 1-AS 1）和对照质粒（shNC）转染到CCA细胞系中。与shNC组相比，转染shFLVCR 1-AS 1的CCA细胞增殖、集落形成、迁移和侵袭能力均受到明显抑制。ShFLVCR 1-AS 1处理后，细胞迁移和侵袭相关蛋白Twist、基质金属蛋白酶（MMP）-2和MMP-9的表达水平也明显降低。此外，FLVCR 1-AS 1敲低抑制异种移植模型中的肿瘤生长。从机制上讲，FLVCR 1-AS 1被证明可以海绵化人CCA中的microRNA-485- 5 p（miR-485- 5 p）。CCA组织中miR-458- 5 p的表达较正常组织明显降低，Pearson相关分析显示CCA组织中FLVCR 1-AS 1的表达与miR-485- 5 p的表达呈负相关。这些结果提示lncRNA FLVCR 1-AS 1可作为CCA的一个新的治疗靶点和潜在的诊断标志物。
Long non-coding RNA (lncRNA) FLVCR1 antisense RNA 1 (FLVCR1-AS1) serves a crucial role in many types of cancer; however, to the best of our knowledge, the biological effect of FLVCR1-AS1 in cholangiocarcinoma (CCA) remains unclear. The present study aimed to elucidate the involvement of FLVCR1-AS1 in the regulation of human CCA cell growth, migration and invasion, as well as the mechanisms underlying its effect. The expression levels of FLVCR1-AS1 in CCA tumor tissues, adjacent normal tissues, CCA cell lines and a cholangiocyte cell line were determined by reverse transcription-quantitative polymerase chain reaction. A significantly higher expression level of FLVCR1-AS1 was identified in CCA tumor tissues and the CCA cell lines HuCCT1 and CCLP1 compared with the normal controls. Short hairpin RNA targeting FLVCR1-AS1 (shFLVCR1-AS1) and a control plasmid (shNC) were transfected into CCA cell lines. Cell proliferation, colony formation, migration and invasion of CCA cells transfected with shFLVCR1-AS1 were significantly suppressed compared with the shNC groups. The expression levels of migration and invasion-associated proteins, including Twist, matrix metalloproteinase (MMP)-2 and MMP-9, were also significantly suppressed by shFLVCR1-AS1-treatment. Furthermore, FLVCR1-AS1 knockdown inhibited tumor growth in a xenograft model. Mechanistically, FLVCR1-AS1 was demonstrated to sponge microRNA-485-5p (miR-485-5p) in human CCA. The expression of miR-458-5p was significantly decreased in CCA tissue compared with normal tissue, and Pearson's correlation analysis revealed that FLVCR1-AS1 expression was negatively correlated with miR-485-5p expression in CCA tissues. These results suggested that lncRNA FLVCR1-AS1 may be used as a novel therapeutic target and a potential diagnostic marker for CCA.