中国耳鼻咽喉颅底外科杂志2026，Vol.32Issue(2)：26-32,7.DOI:10.11798/j.issn.1007-1520.202525149
与GRP78相关的miR-15a-5p在鼻咽癌放疗抵抗中的作用
The role of miR-15a-5p associated with GRP78 in radiotherapy resistance of nasopharyngeal carcinoma
摘要
Abstract
Objective To investigate the role of non-coding microRNA-15a-5p(miR-15a-5p)associated with glucose-regulated protein 78(GRP78)in radioresistance of nasopharyngeal carcinoma and to preliminarily explore the regulatory mechanism between them.Methods The expression of GRP78 in nasopharyngeal carcinoma cells was interfered by shRNA technology.The miRNA related to GRP78 was screened by miRNA chip,and the expression level of miR-15a-5p after knockdown was verified by reverse transcription-polymerase chain reaction.The role of miR-15a-5p in nasopharyngeal carcinoma radiotherapy resistance was verified by transient transfection of miR-15a-5p corresponding mimics and inhibitors in nasopharyngeal carcinoma cell lines.The possible molecular mechanism of GRP78 regulating miR-15a-5p was preliminarily analyzed by bioinformatics.Results The established radioresistant nasopharyngeal carcinoma cell line C666-IR showed stronger resistance to radiation than its parental cell C666-1,and had higher expression and wider distribution of GRP78 protein.The expression of miR-15a-5p in C666-IR cells was higher than that in C666-1 cells.After irradiation,the level of miR-15a-5p remained high in nasopharyngeal carcinoma cells with high expression of GRP78,while knockdown of GRP78 could reduce the level of miR-15a-5p in nasopharyngeal carcinoma cells.Transient transfection of miR-15a-5p mimics enhanced the migration ability and radioresistance of C666-1 cells,while transient transfection of miR-15a-5p inhibitors reduced the migration ability and radioresistance of C666-IR cells.Bioinformatics analysis predicted that the region around the 460 site of the miR-15a-5p gene promoter was most likely to bind to transcription factors,and 13 possible transcription factors were predicted,of which STAT4 and FOXP3 had the greatest possibility.Conclusions GRP78 mediates the up-regulation of miR-15a-5p expression to promote radiotherapy resistance of nasopharyngeal carcinoma.The regulatory mechanism may be that GRP78 increases the expression of miR-15a-5p by driving the transcription factor STAT4/FOXP3.Targeting miR-15a-5p may provide a new therapeutic strategy for radiotherapy-resistant nasopharyngeal carcinoma.关键词
鼻咽癌/葡萄糖调节蛋白78/微小RNA-15a-5p/放疗抵抗Key words
Nasopharyngeal carcinoma/GRP78/miR-15a-5p/Radiotherapy resistance分类
医药卫生引用本文复制引用
莫妍,冯雪萍,吕武武..与GRP78相关的miR-15a-5p在鼻咽癌放疗抵抗中的作用[J].中国耳鼻咽喉颅底外科杂志,2026,32(2):26-32,7.基金项目
国家自然科学基金面上项目(82273486). （82273486）
