长链非编码RNA FOXD2-AS1对舌鳞癌细胞迁移、侵袭的影响

doi:10.19438/j.cjoms.2020.06.005

中国口腔颌面外科杂志 ›› 2020, Vol. 18 ›› Issue (6): 495-500.doi: 10.19438/j.cjoms.2020.06.005

长链非编码RNA FOXD2-AS1对舌鳞癌细胞迁移、侵袭的影响

周光明^*, 梁衍灿^*, 黄子贤, 张彬

中山大学孙逸仙纪念医院口腔颌面外科,广东广州 510120

收稿日期:2020-01-08 修回日期:2020-04-10 出版日期:2020-11-20 发布日期:2020-12-31
通讯作者: 张彬,E-mail:dr_zhangbin2019@163.com
作者简介:周光明(1993-),男,E-mail:marckey_chow@163.com;梁衍灿(1984-),男,E-mail:yancan214@163.com。^#并列第一作者
基金资助:
国家自然科学基金青年项目(81802700)

Effect of long noncoding RNA FOXD2-AS1 on migration and invasion of tongue squamous cell carcinoma: an in vitro study

ZHOU Guang-ming, LIANG Yan-can, HUANG Zi-xian, ZHANG Bin

Department of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University. Guangzhou 510120, Guangdong Province, China

Received:2020-01-08 Revised:2020-04-10 Online:2020-11-20 Published:2020-12-31

摘要/Abstract

摘要： 目的: 研究长链非编码RNA FOXD2-AS1对舌鳞癌(tongue squamous cell carcinoma, TSCC)细胞迁移和侵袭的影响。方法: 利用RT-qPCR检测长链非编码RNA(long noncoding RNA,lncRNA)FOXD2-AS1在35对舌鳞癌临床组织样本中的表达,结合第8版UICC口腔癌TNM分期标准,对样本的临床病理特征信息进行分析。根据癌组织与癌旁组织的RT-qPCR检测数据,建立受试者工作特征曲线(receiver operating characteristic curve,ROC)。在舌鳞癌细胞系SCC-9和CAL-27中,应用siRNA敲低FOXD2-AS1,进行Transwell迁移和侵袭实验、克隆形成实验,分别检测其对舌鳞癌细胞迁移、侵袭及增殖的影响,Western免疫印迹实验检测其对下游信号通路分子的影响。采用SPSS 23.0软件包对数据进行统计分析。结果: RT-qPCR结果表明,与癌旁组织相比,lncRNA FOXD2-AS1在舌鳞癌组织中显著高表达,且其高表达与颈淋巴结转移以及不良临床分期相关。ROC曲线下面积(area under curve, AUC)为0.8122,95%CI为0.7141~0.9103,灵敏度和特异度分别为0.6和0.8857,cutoff值为4.122。在SCC-9和CAL-27中敲低FOXD2-AS1后,Transwell迁移和侵袭实验显示,舌鳞癌细胞的迁移和侵袭能力被抑制;克隆形成实验显示,其对舌鳞癌细胞增殖能力无显著影响。Western免疫印迹实验显示,敲低lncRNA FOXD2-AS1后,Wnt/β-catenin信号通路中β-catenin分子表达下调。结论: lncRNA FOXD2-AS1在舌鳞癌中高表达,其高表达与舌鳞癌颈淋巴结转移以及不良临床分期相关,lncRNA FOXD2-AS1可促进舌鳞癌细胞的迁移侵袭能力,并可能通过Wnt/β-catenin信号通路进行调控。

关键词: 舌鳞状细胞癌, 长链非编码RNA FOXD2-AS1, 迁移, 侵袭, Wnt/β-catenin信号通路

Abstract: PURPOSE: To investigate the effects of long noncoding RNA FOXD2-AS1 on migration and invasion of tongue squamous cell carcinoma (TSCC). METHODS: RT-qPCR was carried out to validate the expression of lncRNA FOXD2-AS1 in 35 paired clinical TSCC tissues, the relationship between FOXD2-AS1 expression and clinicopathological characteristics was analyzed with the 8th version of UICC TNM staging criteria. Receiver operating characteristic curve (ROC) was made according to RT-qPCR data. Transwell migration and invasion, colony formation assays were performed to detect migration, invasion and proliferative ability of TSCC cells after FOXD2-AS1 being downregulated in SCC-9 and CAL-27 cell lines. Western blot was conducted to detect the influence that FOXD2-AS1 downregulation might have on downstream molecules. SPSS 23.0 software package was used to analyze the data. RESULTS: Compared to para-carcinoma tongue tissues, lncRNA FOXD2-AS1 was highly expressed in TSCC tissues and its high expression was associated with cervical lymph node metastasis and poor TNM stages. In ROC, area under curve (AUC) was 0.8122,95% CI was 0.7141-0.9103,sensitivity and specificity were 0.6 and 0.8857, respectively, and the value of cutoff was 4.122. After FOXD2-AS1 being downregulated in SCC-9 and CAL-27 cell lines,Transwell migration and invasion assays revealed that migration and invasion of TSCC cells were inhibited, but the proliferative ability remained unchanged. Western blot indicated that the expression of β-catenin in Wnt/β-catenin signal pathway downregulated after lncRNA FOXD2-AS1 knockdown. CONCLUSIONS: lncRNA FOXD2-AS1 is highly expressed in TSCC, which promotes migration and invasion of TSCC and is associated with cervical lymph node metastasis and poor TNM stages, probably through modulating Wnt/β-catenin signal pathway.

Key words: Tongue squamous cell carcinoma, LncRNA FOXD2-AS1, Migration, Invasion, Wnt/β-catenin signal pathway

中图分类号:

R739.8

周光明, 梁衍灿, 黄子贤, 张彬. 长链非编码RNA FOXD2-AS1对舌鳞癌细胞迁移、侵袭的影响[J]. 中国口腔颌面外科杂志, 2020, 18(6): 495-500.

ZHOU Guang-ming, LIANG Yan-can, HUANG Zi-xian, ZHANG Bin. Effect of long noncoding RNA FOXD2-AS1 on migration and invasion of tongue squamous cell carcinoma: an in vitro study[J]. China J Oral Maxillofac Surg, 2020, 18(6): 495-500.

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长链非编码RNA FOXD2-AS1对舌鳞癌细胞迁移、侵袭的影响

Effect of long noncoding RNA FOXD2-AS1 on migration and invasion of tongue squamous cell carcinoma: an in vitro study

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