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长链非编码RNA FLVCR1-AS1通过海绵吸附miR-485-5p调控人胆管癌细胞的增殖、迁移和侵袭。

lncRNA FLVCR1-AS1 regulates cell proliferation, migration and invasion by sponging miR-485-5p in human cholangiocarcinoma.

作者信息

Bao Wenqing, Cao Feng, Ni Shubin, Yang Jing, Li Haidong, Su Zhenxi, Zhao Bin

机构信息

Department of General Surgery, Shanghai Seventh People's Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200135, P.R. China.

出版信息

Oncol Lett. 2019 Sep;18(3):2240-2247. doi: 10.3892/ol.2019.10577. Epub 2019 Jul 5.

Abstract

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.

摘要

长链非编码RNA(lncRNA)FLVCR1反义RNA 1(FLVCR1-AS1)在多种癌症中发挥关键作用;然而,据我们所知,FLVCR1-AS1在胆管癌(CCA)中的生物学效应仍不清楚。本研究旨在阐明FLVCR1-AS1在调控人CCA细胞生长、迁移和侵袭中的作用及其作用机制。通过逆转录-定量聚合酶链反应测定FLVCR1-AS1在CCA肿瘤组织、癌旁正常组织、CCA细胞系和胆管上皮细胞系中的表达水平。与正常对照相比,在CCA肿瘤组织以及CCA细胞系HuCCT1和CCLP1中鉴定出FLVCR1-AS1的表达水平显著更高。将靶向FLVCR1-AS1的短发夹RNA(shFLVCR1-AS1)和对照质粒(shNC)转染到CCA细胞系中。与shNC组相比,转染shFLVCR1-AS1的CCA细胞的增殖、集落形成、迁移和侵袭均受到显著抑制。shFLVCR1-AS1处理还显著抑制了包括Twist、基质金属蛋白酶(MMP)-2和MMP-9在内的迁移和侵袭相关蛋白的表达水平。此外,FLVCR1-AS1敲低抑制了异种移植模型中的肿瘤生长。机制上,已证明FLVCR1-AS1在人CCA中可吸附微小RNA- 485-5p(miR-485-5p)。与正常组织相比,CCA组织中miR-485-5p的表达显著降低,Pearson相关性分析显示CCA组织中FLVCR1-AS1表达与miR-485-5p表达呈负相关。这些结果表明,lncRNA FLVCR1-AS1可能作为CCA的新型治疗靶点和潜在诊断标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09e9/6676717/f8df19b0f63b/ol-18-03-2240-g00.jpg

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