长链非编码RNA MNX1-AS1在头颈鳞癌中的生物学功能及临床意义  

Biological Functions and Clinical Significance of Long Non-coding RNA MNX1-AS1 in Head and Neck Squamous Cancer

作　　者：田然 买尔哈巴·米吉提 张相民 吴勇延[2,3] 高伟 Tian Ran;Maierhaba Mijiti;Zhang Xiangmin;Wu Yongyan;Gao Wei(College of Basic Medical Sciences,Shanxi Medical University,Taiyuan 030001,Shanxi,China;Shanxi Key Laboratory of Otolaryngology-Head and Neck Cancer/Department of Otolaryngology-Head and Nech Surgery,First Hospital of Shanxi Medical University,Taiyuan 030001,Shanxi,China;Department of Otolaryngology-Head and Neck Surgery,Longgang Otolaryngology Hospital,Shenzhen 518172,Guangdong,China)

机构地区：[1]山西医科大学基础医学院,太原030001 [2]山西医科大学第一医院耳鼻咽喉头颈肿瘤山西省重点实验室/耳鼻咽喉外科,太原030001 [3]深圳市龙岗区耳鼻咽喉医院耳鼻咽喉头颈外科,广东深圳518172

出　　处：《肿瘤预防与治疗》2023年第4期280-287,共8页Journal of Cancer Control And Treatment

基　　金：广东省基础与应用基础研究基金(编号:2023A1515010342);深圳市科技计划(编号:RCJC20210706091950028、JCYJ20220531102815036)。

摘　　要：目的:明确长链非编码RNA(long non-coding RNA,lnc RNA)MNX1-AS1表达水平与头颈鳞癌患者临床病理参数的关系,阐明lnc RNA MNX1-AS1在头颈癌细胞中发挥的生物学功能,为头颈鳞癌诊疗及预后评估提供潜在分子标志物。方法:分析TCGA数据库头颈鳞癌转录组数据中lnc RNA MNX1-AS1的表达情况;采用实时荧光定量PCR检测人胚肺二倍体细胞2BS和人类永生化表皮细胞Ha Ca T,头颈鳞癌细胞系FD-LSC-1、CAL-27和Detroit562中lnc RNA MNX1-AS1的表达水平,使用RNAi(RNA interference)技术敲降头颈鳞癌细胞中lnc RNA MNX1-AS1的表达,利用CCK-8、平板克隆、流式细胞术、Transwell迁移和侵袭等实验检测lnc RNA MNX1-AS1被敲降后肿瘤细胞系恶性表型的变化。结果:头颈鳞癌组织中lnc RNA MNX1-AS1表达水平高于正常对照组织(头颈鳞癌组织vs正常对照组织=0.323 vs0.088,P<0.05);其表达水平与头颈鳞癌患者病理学分级呈正相关(P<0.05)。生存分析发现,lnc RNA MNX1-AS1高表达组的患者总生存率显著低于低表达组患者(P<0.05);其中位生存时间分别为42.97个月、61.27个月。临床相关性分析发现,有吸烟史患者组中其表达水平高于无吸烟史患者组(P<0.05);临床中晚期患者组中其表达水平高于早中期患者组(P<0.05)。敲降lnc RNA MNX1-AS1可抑制头颈鳞癌细胞增殖、克隆形成、迁移和侵袭能力(均P<0.05)。结论:Lnc RNA MNX1-AS1高表达与头颈鳞癌恶性进展相关,具有促进头颈鳞癌细胞增殖、迁移、侵袭的重要生物学功能,是头颈鳞癌潜在的重要分子标志物。Objective:To investigate the relationship between the expression level of long-non-coding RNA(lncRNA)MNX1-AS1 and the clinicopathological parameters of patients with head and neck cancer(HNC),and clarify the biological function of lncRNA MNX1-AS1in HNC cells,providing a potential biomarker for the diagnosis,treatment,and prognosis evaluation of HNC.Methods:The expression level of lncRNA MNX1-AS1 in the HNC was analyzed using transcriptome sequencing data from TCGA database.The expression levels of lncRNA MNX1-AS1 in human embryonic lung diploid cells 2BS and HaCaT,HNC cell lines FD-LSC-1,CAL-27 and Detroit562 were determined by quantitative real-time PCR.RNAi(RNA interference)was introduced for lncRNA MNX1-AS1 knockdown in HNC cell lines,and the biological functions were examined by CCK-8,clone formation,flow cytometry,and Transwell invasion and migration assays.Results:LncRNA MNX1-AS1 was up-regulated in HNC cell lines(HNC tissue vs normal tissue=0.323 vs 0.088,P 0.005),and the level of lncRNA MNX1-AS1 was positively correlated with the pathological grade(P<0.05).The overall survival of the lncRNA MNX1-AS1 high group was significantly lower than that of the lncRNA MNX1-AS1 low group(P<0.05),and the median survival time of the two groups were 42.97 months and 61.27 months(P<0.05).The correlation analysis showed that the expression level of lncRNA MNX1-AS1 in patients with smoking history was higher than that of patients without smoking history(P<0.05);and that in patients the with advanced clinical stage was higher than that in patients with early and middle stages(P<0.05).Knockdown of LncRNA MNX1-AS1 inhibited the proliferation,cloning,migration and invasion of HNC cells(all P<0.05).Conclusion:High level of lncRNA MNX1-AS1 is associated with the malignant progression of HNC.LncRNA MNX1-AS1 promotes the important biological functions of proliferation,migration and invasion in HNC cells.Therefore,lncRNA MNX1-AS1 may serve as a potential biomarker for HNC.

关 键 词：头颈鳞状细胞癌 癌基因 长链非编码RNA LncRNA MNX1-AS1 侵袭转移 

分 类 号：Q74[生物学—分子生物学] R739.6[医药卫生—肿瘤]