miR-214-5p通过FANCA调节神经母细胞瘤DNA损伤和化疗敏感性

doi:10.3870/j.issn.1672-8009.2025.06.004

医学分子生物学杂志 ›› 2025, Vol. 22 ›› Issue (6): 557-562.doi: 10.3870/j.issn.1672-8009.2025.06.004

miR-214-5p通过FANCA调节神经母细胞瘤DNA损伤和化疗敏感性

赵聪慧¹, 刘冰², 刘佳佳³, 崔凌⁴, 刘晓霞⁵, 雷建华²

邯郸市中心医院¹康复医学科,²神经内科,³神经外五科,⁴放疗一科,⁵免疫二科河北省邯郸市,056000

收稿日期:2025-04-24 出版日期:2025-11-30 发布日期:2025-12-25
通讯作者: 刘冰(E-mail:13784221106@163.com)
基金资助:
河北省医学科学研究课题(No.20241660)

Effect of miR-214-5p on DNA Damage and Chemotherapy Sensitivity in Neuroblastoma Cells by Regulation of FANCA

ZHAO Conghui¹, LIU Bing², LIU Jiajia³, CUI Ling⁴, LIU Xiaoxia⁵, LEI Jianhua²

¹Department of Rehabilitation Medicine,²Department of Neurology,³the Fifth Department of Neurosurgery,⁴the First Department of Radiotherapy,⁵the Second Department of Immunology,Handan Central Hospital,Handan,Hebei,056000,China

Received:2025-04-24 Online:2025-11-30 Published:2025-12-25
Contact: LIU Bing(E-mail:13784221106@163.com)
Supported by:
Medical Science Research Project of Hebei Province(No.20241660)

摘要/Abstract

摘要： 目的探讨微小RNA-214-5p(miR-214-5p)对神经母细胞瘤(NB)DNA损伤和化疗敏感性的调控作用及机制。方法通过TARGET数据库分析范可尼贫血互补组A型(fanconi anemia complementary group A protein,FACNA)蛋白与NB临床病理特征的关系。构建miR-214-5p低表达、FANCA过/低表达NB细胞系,采用细胞计数试剂盒-8(CCK-8)、移植瘤模型检测其表达对NB体内外增殖的影响,并验证miR-214-5p与FANCA靶向关系。结果 GEO数据库和TARGET数据库中筛查出与NB相关的交集基因为FANCA,其表达与调节细胞增殖基因、预后及临床病理特征密切相关(P<0.05)。与空载体(Vector)组比较,FANCA组细胞活力、移植瘤体积和重量升高(P<0.05);与shNC组比较,shFANCA1组、shFANCA2组细胞活力降低(P<0.05);与对照组比较,1 mmol/L过氧化氢(H₂O₂)处理后磷酸化组蛋白γ-H2AX升高(P<0.05),但FANCA过表达后γ-H2AX降低(P<0.05)。随着多柔比星浓度增加,细胞活力降低,但FANCA组细胞活力高于Vector组(P<0.05)。miR-214-5p与FANCA存在靶向关系。结论 miR-214-5p可靶向降低FANCA表达抑制NB细胞增殖,参与细胞DNA损伤和化疗敏感性调控。

关键词: 神经母细胞瘤, 微小RNA-214-5p, 范可尼贫血互补组A型蛋白, DNA损伤, 化疗敏感性

Abstract: Objective To explore the effect and mechanism of microRNA-214-5p(miR-214-5p)on DNA damage and chemotherapy sensitivity in neuroblastoma(NB). Methods The relationship between Fanconi anemia complementary group A (FACNA) protein and clinicopathological characteristics of NB was analyzed by TARGET database.NB cell lines with low expression of miR-214-5p and overexpression/low expression of FANCA were constructed,and their effects on the proliferation of NB in vivo and in vitro were detected by cell counting kit-8(CCK-8)and transplanted tumor model.The targeted relationship between miR-214-5p and FANCA was verified. Results FANCA was screened out as the intersection gene correlated with NB in GEO and TARGET databases,and its expression level was related to cells proliferation pathways,and the prognosis and clinicopathological characteristics of NB.Compared with those in the empty vector(Vector)group,the cells viability,and the volume and weight of transplanted tumors were increased in the FANCA group(P<0.05).Compared with those in the shNC group,the cells viability was decreased in the shFANCA1/2 groups(P<0.05).Compared with those in the control group,the phosphorylated histone γ-H2AX was increased after treated with 1 mmol/L H₂O₂(P<0.05),but γ-H2AX was decreased after FANCA overexpression(P<0.05).With the increase of doxorubicin concentration,cells viability was decreased,but it was higher in the FANCA group than in the Vector group(P<0.05).There was a targeted relationship between miR-214-5p and FANCA. Conclusion miR-214-5p can inhibit the proliferation of NB cells by reducing FANCA expression level,and regulate the DNA damage and chemotherapy sensitivity in cells.

Key words: neuroblastoma, microRNA-214-5p, fanconi anemia complementary group A protein, DNA damage, chemotherapy sensitivity

中图分类号:

R739.4

赵聪慧, 刘冰, 刘佳佳, 崔凌, 刘晓霞, 雷建华. miR-214-5p通过FANCA调节神经母细胞瘤DNA损伤和化疗敏感性[J]. 医学分子生物学杂志, 2025, 22(6): 557-562.

ZHAO Conghui, LIU Bing, LIU Jiajia, CUI Ling, LIU Xiaoxia, LEI Jianhua. Effect of miR-214-5p on DNA Damage and Chemotherapy Sensitivity in Neuroblastoma Cells by Regulation of FANCA[J]. Journal of Medical Molecular Biology, 2025, 22(6): 557-562.

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miR-214-5p通过FANCA调节神经母细胞瘤DNA损伤和化疗敏感性

Effect of miR-214-5p on DNA Damage and Chemotherapy Sensitivity in Neuroblastoma Cells by Regulation of FANCA

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