摘要
目的探讨环状RNA(circRNA)hsa_circ_0038817在头颈部鳞状细胞癌(HNSCC)中的表达及作用机制。方法采用RNA测序技术分析HNSCC中circRNA的表达谱,并通过生物信息学分析、Sanger双脱氧链终止法测序和实时荧光定量聚合酶链反应验证其环状结构及表达模式。通过克隆形成实验、划痕实验和Transwell实验评估hsa_circ_0038817对细胞生长和增殖的影响。利用microRNA靶基因数据库筛选、荧光素酶报告基因实验和蛋白质印迹法探究hsa_circ_0038817调控HNSCC侵袭的潜在机制。结果在HNSCC中,hsa_circ_0038817在肿瘤组织和细胞中表达水平显著升高,其环状结构得到验证。高表达hsa_circ_0038817的患者总体生存率较低,且其表达水平与临床分期、淋巴结转移和生存状态有关。体外实验证实,敲低hsa_circ_0038817可抑制HNSCC细胞的迁移、侵袭能力以及上皮-间质转化过程。从作用机制上看,hsa_circ_0038817通过作为miR-203的分子海绵下调高迁移率族蛋白A2(HMGA2)的表达,从而促进HNSCC的进展。结论hsa_circ_0038817在HNSCC组织中高表达,并通过竞争性内源RNA调控机制与miR-203/HMGA2轴相互作用,促进HNSCC细胞增殖。这些发现表明,hsa_circ_0038817可作为HNSCC预后的生物标志物及潜在治疗靶点。
Objective To explore the expression of circular RNA(circRNA)hsa_circ_0038817 in head and neck squamous cell carcinoma(HNSCC)and its potential regulatory mechanisms.Methods RNA sequencing was employed to illustrate the expression profile of circRNAs in HNSCC.Subsequently,bioinformatics analysis,sequencing by Sanger dideoxychain termination method,and quantitative real-time PCR were utilized to ascertain the ring-forming traits of RNA and dissect its expression patterns.The influence of hsa_circ_0038817 on cell growth and proliferation was appraised through colony formation assays,wound healing assays,and Transwell assays.Additionally,microRNA target gene database screening,luciferase reporter gene assays,and Western blotting were used to probe into the underlying mechanism of hsa_circ_0038817 regulating HNSCC invasion.Results In the context of HNSCC,hsa_circ_0038817 exhibited an obviously elevated expression level both in cancer tissues and cells,and its loop structure was verified.The overall survival was low in patients with high hsa_circRNA_0038817 expression level with the expression level closely related to the clinical stage,and lymph-node metastasis and living status.Meanwhile,in vitro experiments validated that the knockdown of hsa_circ_0038817 led to the suppression of HNSCC cell migratory and invasive capabilities,as well as the epithelial-to-mesenchymal transition process.From the perspective of mechanism,hsa_circ_0038817 down-regulated the expression of high mobility group AT-hook 2(HMGA2)byacting as a molecular sponge of miR-203,thereby facilitating the progression of HNSCC.Conclusion hsa_circ_0038817 is highly expressed in HNSCC tissues,and interacts with the miR-203/HMGA2 axis through a competitive endogenous RNA regulatory mechanism,promoting HNSCC cell proliferation.These findings suggest that hsa_circ_0038817 may serve as both a prognostic biomarker and a potential therapeutic target for HNSCC.
作者
李群
许雨欣
史晨雪
邬振华
王剑
沈志森
LI Qun;XU Yuxin;SHI Chenxue;WU Zhenhua;WANG Jian;SHEN Zhisen(Department of Otorhinolaryngology Head and Neck Surgery,the Affiliated Lihuili Hospital,Ningbo University,Ningbo 315000,China;不详)
出处
《浙江医学》
2025年第12期1263-1271,共9页
Zhejiang Medical Journal
基金
浙江省医药卫生科技计划项目(2024KY282)
宁波市医疗卫生高端团队重大攻坚项目(2023030514)
宁波市临床医学研究中心项目(2022L005)
宁波市医疗中心李惠利医院“惠利基金”(2022ZD001)。
