miR-589-3p靶向DSPP基因对口腔鳞状细胞癌肿瘤干细胞的调控作用  

Effects of miR-589-3p in regulating cancer stem cells of oral squamous cell carcinoma through targeting DSPP

作　　者：游东乐 全海薇 全海英(指导)[1] YOU Dongle;QUAN Haiwei;QUAN Haiying(Department of Stomatology,Affiliated Hospital of Jilin Medical University,Jilin 132000,China)

机构地区：[1]吉林医药学院附属医院口腔科,吉林132000 [2]北华大学医学技术学院,吉林132013

出　　处：《中国免疫学杂志》2022年第1期61-66,共6页Chinese Journal of Immunology

基　　金：吉林省教育厅“十三五”科学技术项目(JJKH20180834KJ)。

摘　　要：目的:探讨miR-589-3p靶向牙本质涎磷蛋白(DSPP)对口腔鳞状细胞癌(OSCC)肿瘤干细胞增殖、凋亡、侵袭的影响。方法:对OSCC患者和口腔良性肿物患者组织中miR-589-3p和DSPP的表达进行检测,对miR-589-3p和DSPP的相关性进行分析。双荧光素酶报告实验验证miR-589-3p与DSPP的靶向关系。免疫磁珠分选技术分选OSCC肿瘤干细胞,干预肿瘤干细胞中miR-589-3p和DSPP的表达,将细胞分为mimics control组、mimics miR-589-3p组、inhibitors control组、inhibitors miR-589-3p组、mimics miR-589-3p+pcDNA-DSPP组。随后检测各组上皮间质转化相关因子的表达。MTT、Transwell和流式细胞术分别用来检测各组细胞增殖活力、侵袭以及细胞凋亡情况。结果:相对于口腔黏膜良性肿物患者,OSCC患者miR-589-3p表达下降,DSPP表达增强,miR-589-3p与DSPP表达呈负相关(均P<0.05)。相对于mimics control组,mimics miR-589-3p组中细胞凋亡增多,细胞增殖、侵袭以及上皮间质转化相关因子的表达被抑制(均P<0.05)。相对于inhibitors control,inhibitors miR-589-3p组中细胞凋亡减少,细胞增殖、侵袭以及上皮间质转化相关因子的表达增多(均P<0.05)。miR-589-3p模拟物对OSCC肿瘤干细胞的作用能够被DSPP过表达逆转。结论:miR-589-3p可靶向抑制DSPP,进而抑制OSCC肿瘤干细胞的增殖、侵袭并促进其凋亡。Objective:To explore the effects of miR-589-3 p on proliferation,apoptosis and invasion of cancer stem cells of oral squamous cell carcinoma(OSCC)via targeting dentin sialophosphoprotein(DSPP).Methods:The expression of miR-589-3 p and DSPP in OSCC patients and patients with benign oral masses were detected,the relevance between miR-589-3 p and DSPP was analyzed. Dual luciferase reporter gene assay was adopted to confirm the targeting relationship between miR-589-3 p and DSPP. Tumor stem cells were isolated through using technologies of immune-magnetic beads,expression of miR-589-3 p and DSPP in tumor stem cells was intervened and the cells were grouped. Subsequently the expression of epithelial stromal transformation related factors in each group was detected. MTT,Transwell assay and Flow cytometry were utilized to detect cell proliferation,invasion and apoptosis.Results:Compared with patients with benign oral masses,expression of miR-589-3 p in OSCC patients was down-regulated while DSPP expression was up-regulated,the expression of miR-589-3 p was in negative correlation to DSPP(all P<0.05). Compared with mimics control group,cell apoptosis was increased while proliferation,invasion and expression of epithelial stromal transformation related factors were inhibited in mimics miR-589-3 p group(all P<0.05). Compared with inhibitors control group,cell apoptosis was down-regulated while proliferation,invasion and expression of epithelial stromal transformation related factors were up-regulated in inhibitors miR-589-3 p group(all P<0.05). The effects of mimics miR-589-3 p on OSCC cancer stem cells could be reversed by DSPP overexpression.Conclusion:miR-589-3 p has the ability to inhibit the proliferation and invasion of OSCC cancer stem cells while accelerate it′s apoptosis through targeting DSPP.

关 键 词：miR-589-3p 牙本质涎磷蛋白 口腔鳞状细胞癌 肿瘤干细胞 

分 类 号：R739.8[医药卫生—肿瘤]