目的：探讨miR-423-5p在人脑神经胶质瘤组织和细胞中的表达及其调控程序性细胞死亡蛋白5（programmed cell death protein 5，PDCD5）增强胶质瘤细胞对替莫唑胺（temozolomide，TMZ）的耐药性。方法：收集2017年1月至2018年12月北 华大学附属医院神经外科手术切除的20例脑神经胶质瘤患者的瘤及瘤旁组织标本，以及胶质瘤细胞系U251、 U87、SHG-44和人 脑小胶质细胞株HMC-3， 用qPCR法检测胶质瘤组织及细胞系中miR-423-5p和PDCD5的表达水平。用合成的miR-423-5p mimics 和miR-NC分别转染U251和U87细胞，同时用不同浓度（50、100、150和200 μmol/L）的TMZ处理细胞，检测转染细胞对TMZ的 耐药性，用MTT法、克隆形成实验检测转染细胞的增殖活力，用Western blotting检测U251、 U87细胞中c-caspase 3、Bcl-2和 PDCD5蛋白的表达。用双荧光素酶报告基因实验验证 miR-423-5p 与 PDCD5 的靶向关系。结果：miR-423-5p 在脑神经胶质 瘤组织和胶质瘤细胞系中均高表达（均P<0.01）。与miR-NC组比较，miR-423-5p mimics组U251和U87细胞的增殖能力明显增 强（均P<0.01）， 对TMZ的耐药性增强。双荧光素酶报告基因实验证实miR-423-5p可与PDCD5 3' UTR结合，抑制PDCD5的表 达。结论：miR-423-5p高表达增强胶质瘤细胞对TMZ的耐药能力，其可作为临床胶质瘤治疗的潜在新靶点。

Objective: To investigate the miR-423-5p expression in brain glioma tissues and cell lines, and its promotive effect on temozolomide (TMZ) chemoresistance by targeting PDCD5 (programmed cell death protein 5). Methods: Tumor tissues and matched peritumoral tissues were collected from 20 brain glioma patients who were surgically treated in the Department of Neurosurgery, Affiliated Hospital of Beihua University between January 2017 and December 2018. Glioblastoma cell lines (U251, U87, SHG-44) and human normal glial cell line HMC-3 were also used in the study. The relative expression of miR-423-5p and PDCD5 in brain glioma and peritumoral tissues andcelllineswasdetected by qPCR.ThesynthesizedmiR-423-5p mimics and miR-NC were respectively transfected into U251 and U87 cells; meanwhile,TMZatdifferentconcentrations (50, 100, 150 and 200 μmol/L) werealsousedtotreat thecells. Then, the chemoresistance of cells to TMZ were determined. MTT assayandcolonyformationassaywereusedtoexaminethe proliferationofU251andU87cells,andWesternblotting was used to detect the expression of c-caspase 3, Bcl-2 and PDCD5 proteins in U251 and U87 cells. The targeting relationship between PDCD5 and miR-423-5p was validated through Dual luciferasereportergene assay. Results: miR-423-5p was highly expressed in glioma tissues and glioma cell lines (all P<0.01). As compared with the miR-NC group, the proliferation and TMZ-chemoresistance of U251 and U87 cells in miR-423-5p mimics group significantly increased (all P<0.01). Dual luciferase reporter gene assay validated that miR-423-5p could bind with PDCD5 3' UTR to suppress the expression of PDCD5. Conclusion: High expression of miR-423-5p enhances the chemoresistance of glioma cells to TMZ, and miR-423-5p may serve as a potential therapeutic target in the treatment of brain glioma.

吉林省教育厅“十三五计划”科学技术项目（No. JJKH20180332KJ）