摘要
目的 基于公共数据库探索微小RNA (miRNA) 200a/141、信号转导和转录激活因子4 (STAT4)在口腔鳞状细胞癌(OSCC)中的表达及临床意义并构建预后模型,探讨其作为潜在治疗靶点的可行性。通过体外实验验证仿生明胶外泌体颗粒递送miRNA200a/141进而调节STAT4,评估在OSCC的细胞和分子水平上的核酸保护能力及抗癌作用。方法 通过癌症基因组图谱数据库下载OSCC相关miRNA及信使RNA表达测序数据,使用R语言进行数据分析,评估miRNA200a/141与STAT4的表达水平和临床相关性。制备负载miRNA200a/141的仿生明胶外泌体纳米颗粒(GNP-EXO-miRNA200a/141),进行Transwell迁移、细胞划痕和四甲基偶氮唑蓝实验,评估纳米颗粒对SCC25细胞的作用,并通过定量聚合酶链式反应和蛋白质免疫印迹法检测其对SCC25细胞中STAT4表达的影响。结果 miRNA200a/141在OSCC组织中的表达水平显著降低,而其靶标STAT4的表达水平升高,两者呈负相关。制备的GNP-EXO-miRNA200a/141纳米颗粒具有良好的粒径分布和稳定性。在细胞实验中,GNPEXO-miRNA200a/141显著抑制了SCC25细胞的增殖和迁移,并显著下调了STAT4的表达。结论 miRNA200a/141通过调节STAT4在OSCC中发挥重要作用,其有望成为OSCC的诊断、治疗和预后的潜在的分子标志物和治疗靶点。
Objective This study aimed to explore the expression and clinical significance of mircoRNA(miRNA)200a/141 and signal transducer and activator of transcription 4(STAT4)in oral squamous cell carcinoma(OSCC)and construct a prognostic model to explore its feasibility as a potential therapeutic target.In vitro experiments verified that bionic gelatin exosome particles delivered mi-RNA200a/141 to regulate STAT4.This study also aimed to evaluate the protective capacity and anticancer effects of nucleic acids at the cellular and molecular levels of OSCC.Methods OSCC-related miRNA-sequencing and messenger RNA-sequencing data were downloaded from The Cancer Genome Atlas database.Data analysis was performed using R language to assess the expression levels and clinical correlation of miRNA200a/141 with STAT4.Biomimetic gelatin exosome nanoparticles(GNP-EXO-mi-RNA200a/141)loaded with miRNA were prepared,and Transwell migration assay,cell scratch assay,and methyl thiazolyl tetrazolium assay were performed to evaluate the effect of nanoparticles on SCC25 cells.The effects of the nanoparticles on STAT4 expression in SCC25 cells were examined using quantitative polymerase chain reaction and Western blot.Results The expression of miRNA200a/141 was significantly reduced in OSCC tissues,whereas that of its target STAT 4 increased,which was inversely correlated.The prepared GNP-EXO-miRNA200a/141 nanoparticles showed good size distribution and stability.In cell experiments,GNP-EXO-miRNA200a/141 significantly inhibited the proliferation and migration of SCC25 cells and significantly downregulated STAT4 expression.Conclusion miRNA200a/141 plays an important role in OSCC by regulating STAT4,and it is expected to be a potential molecular marker and therapeutic target for the diagnosis,treatment,and prognosis of OSCC.
作者
姚曼曼
仇永乐
刘铁军
路月亭
路华林
尚宏悦
董博
Yao Manman;Qiu Yongle;Liu Tiejun;Lu Yueting;Lu Hualin;Shang Hongyue;Dong Bo(Dept.of Stomatology,the Fourth Hospital,Hebei Medical University,Shijiazhuang 050000,China)
出处
《国际口腔医学杂志》
北大核心
2025年第4期473-483,共11页
International Journal of Stomatology
基金
河北省中医药管理局项目(2024050)
河北省自然科学基金面上项目(H2024206476)
中央引导地方科技发展资金项目(246Z7762G)。
作者简介
姚曼曼,主治医师,硕士,Email:49103567@hebmu.edu.cn;通信作者:仇永乐,副主任医师,博士,Email:qiuyongle@163.com。
