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中国生物工程杂志

CHINA BIOTECHNOLOGY
中国生物工程杂志  2024, Vol. 44 Issue (1): 98-106    DOI: 10.13523/j.cb.2309023
综述     
MicroRNA调控在溶瘤病毒疗法中的应用与展望*
赵灿阳1(),林燕真2,程通3,王玮1,***()
1 厦门大学公共卫生学院 国家传染病诊断试剂与疫苗工程技术研究中心 厦门 361102
2 厦门大学附属中山医院 厦门 361004
3 厦门大学生命科学学院 厦门 361102
Application of MicroRNA Regulation in Oncolytic Virotherapy and Its Prospects
Canyang ZHAO1(),Yanzhen LIN2,Tong CHENG3,Wei WANG1,***()
1 National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Pulic Health,Xiamen University, Xiamen 361102, China
2 Affiliated Zhongshan Hospital, Xiamen University, Xiamen 361004, China
3 School of Life Sciences, Xiamen University, Xiamen 361102, China
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摘要:

MicroRNA(miRNA)是一类内源性的、能够特异性调控真核生物细胞内转录后基因表达的非编码单链RNA。近年来,miRNA的调控作用已被广泛应用于溶瘤病毒的设计。一方面,通过在病毒基因组中插入肿瘤内表达下调的组织特异性miRNA的靶序列,可以改变溶瘤病毒的组织趋向性,在达到减毒效果的同时保留其抗肿瘤活性。另一方面,通过在病毒基因组中插入表达天然或人工改造的miRNA,可以促进病毒复制,改善肿瘤微环境,从而增强溶瘤病毒的疗效。讨论目前miRNA调控在溶瘤病毒领域中的应用进展,为优化溶瘤病毒疗法策略提供参考。

关键词: MicroRNA溶瘤病毒靶向调控病毒治疗    
Abstract:

MicroRNAs (miRNAs) are a type of endogenous, non-coding, single-stranded RNA that specifically regulates post-transcriptional gene expression in eukaryotic cells. In recent years, miRNA regulation has been utilized in the design of oncolytic viruses. By inserting a target sequence of a tissue-specific miRNA that is down-regulated in the tumor into the viral genome, the tissue tropism of the oncolytic virus can be altered, and the anti-tumor activity of the virus can be remained during viral attenuation. Additionally, natural or artificially modified miRNAs can be inserted and expressed in viral genomes to promote viral replication and improve the tumor microenvironment, thereby enhancing the therapeutic effect of oncolytic viruses. This paper reviews and discusses the utilization of miRNA regulation in oncolytic virology, with the aim of providing insights into the optimization of existing oncolytic virotherapy strategies.

Key words: MicroRNA    Oncolytic virus    Targeted regulation    Virotherapy
收稿日期: 2023-09-20 出版日期: 2024-02-04
ZTFLH:  Q789  
基金资助: *福建省自然科学基金(2022J011352)
通讯作者: ***电子信箱:lukewang@xmu.edu.cn   
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引用本文:

赵灿阳, 林燕真, 程通, 王玮. MicroRNA调控在溶瘤病毒疗法中的应用与展望*[J]. 中国生物工程杂志, 2024, 44(1): 98-106.

Canyang ZHAO, Yanzhen LIN, Tong CHENG, Wei WANG. Application of MicroRNA Regulation in Oncolytic Virotherapy and Its Prospects. China Biotechnology, 2024, 44(1): 98-106.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/10.13523/j.cb.2309023        https://manu60.magtech.com.cn/biotech/CN/Y2024/V44/I1/98

组织部位 miRNAs
血液 hsa-miR-486-5p、hsa-miR-451a、hsa-miR-92a-3p、hsa-miR-191-5p
骨骼 hsa-miR-10b-5p、hsa-miR-143-3p、hsa-miR-100-5p、hsa-let-7a-5p、hsa-miR-21-5p、hsa-miR-191-5p、hsa-miR-22-3p
心脏 hsa-miR-1-3p、hsa-miR-143-3p、hsa-miR-133a-3p、hsa-miR-27b-3p、hsa-miR-99a-5p
肝脏 hsa-miR-148a-3p、hsa-miR-22-3p、hsa-miR-122-5p、hsa-miR-143-3p、hsa-miR-21-5p、hsa-miR-192-5p、hsa-miR-101-3p、hsa-let-7a-5p、hsa-miR-10a-5p
hsa-miR-143-3p、hsa-miR-21-5p、hsa-miR-30a-5p、hsa-miR-22-3p、hsa-miR-101-3p、hsa-miR-30a-3p、hsa-miR-10a-5p、hsa-let-7a-5p、hsa-miR-148a-3p、hsa-miR-99b-5p、hsa-let-7b-5p、hsa-miR-103a-3p
hsa-miR-10b-5p、hsa-miR-30a-5p、hsa-miR-143-3p、hsa-miR-10a-5p、hsa-miR-22-3p、hsa-miR-30a-3p、hsa-miR-21-5p、hsa-let-7a-5p、hsa-miR-99b-5p、hsa-miR-26a-5p
胰腺 hsa-miR-21-5p、hsa-miR-143-3p、hsa-miR-22-3p、hsa-miR-148a-3p、hsa-let-7a-5p、hsa-miR-10a-5p、hsa-miR-375-3p、has-miR-216a/b、has-miR-217
大脑 hsa-miR-26a-5p、hsa-miR-181a-5p、hsa-let-7a-5p、hsa-miR-16-5p、hsa-miR-9-5p、hsa-miR-99a-5p、hsa-miR-143-3p、hsa-miR-100-5p、hsa-let-7f-5p、hsa-miR-27b-3p、hsa-miR-22-3p、hsa-miR-128-3p
结肠 hsa-miR-143-3p、hsa-miR-192-5p、hsa-miR-375-3p、hsa-miR-10b-5p、hsa-miR-10a-5p、hsa-let-7b-5p、hsa-miR-92a-3p、hsa-miR-99b-5p、hsa-miR-26a-5p、hsa-let-7a-5p
直肠 hsa-miR-143-3p、hsa-miR-192-5p、hsa-miR-10b-5p、hsa-miR-10a-5p、hsa-miR-21-5p、hsa-miR-26a-5p、hsa-let-7a-5p、hsa-miR-181a-5p
前列腺 hsa-miR-143-3p、hsa-miR-21-5p、hsa-miR-99a-5p、hsa-miR-148a-3p、hsa-miR-26a-5p
子宫内膜 hsa-miR-143-3p、hsa-miR-10b-5p、hsa-let-7a-5p、hsa-miR-21-5p、hsa-miR-10a-5p、hsa-let-7b-5p、hsa-miR-22-3p、hsa-miR-101-3p
膀胱 hsa-miR-143-3p、hsa-miR-21-5p、hsa-miR-22-3p、hsa-miR-10b-5p、hsa-let-7a-5p
肌肉 hsa-miR-1-3p、hsa-miR-133a-3p、hsa-miR-378a-3p、hsa-miR-143-3p、hsa-miR-26a-5p
表1  人体特定组织中富集的miRNA
肿瘤类型 表达下调的miRNA 表达上调的miRNA
头颈癌 miR-195-5p、miR-101-3p、miR-136-3p、miR-145-3p、miR-375 miR-615-3p、miR-503-3p、miR-21-5p、miR-455-3p、miR-93-5p
乳腺癌 Let-7-7c-5p、miR-1-3p、miR-30e-3p、miR-139-5p、miR-486-5p miR-592、miR-21-5p、miR-7-5p、miR-183-3p、miR-3610
肺癌 miR-7641、miR-6788-3p、miR202-3p、miR-6808-3p、miR-433-3p miR-153-5p、miR-301a-5p、miR-33b-p、miR-592、miR-577
胃癌 miR-139-5p、miR-133b、miR-139-3p、miR-145-3p、miR-1-3p miR-21-5p、miR-3662、miR-25-5p、miR-135b-5p、miR-21-3p
结直肠癌 Let-7d-3p、miR-5196-3p、miR-4743-5p、miR-328-3p、miR-139-5p Let-7f-1-3p、miR-590-5p、miR-889-3p、miR-455-5p、miR-18a-5p
膀胱癌 miR-139-3p、miR-1-3p、miR-30a-3p、miR-383-5p、miR-133b Let-7f-2-3p、miR-183-3p、miR-33b-5p、miR-147b、miR-210-5p
肾癌 miR-891a-5b、miR-10b-5p、miR-184、miR-141-3p、miR-145-5p miR-21-5p、miR-7156-5p、miR-21-3p、miR-93-5p、miR-25-3p
表2  miRNA在不同肿瘤组织中的特异性表达谱
病毒类型 miRNA 拷贝数 靶器官 插入位置 肿瘤模型 参考文献
柯萨奇病毒
A21型
miR-133、miR-206 2 肌肉 基因组的3'-UTR 骨髓瘤 [22]
miR-133、miR-206 2 肌肉 基因组的5'-UTR 黑色素瘤 [23]
柯萨奇病毒
B3型
miR-375 3 胰腺 基因组的5'-UTR
和3'-UTR
结直肠癌 [24]
miR-34a 4 胰腺 基因组的5'-UTR
和3'-UTR
肺癌 [25]
miR-1、miR-216、
miR-143、miR-145
2~4 心脏、肌肉、胰腺 基因组的5'-UTR 乳腺癌 [26]
门戈病毒 miR-124、miR-133b、
miR-208a
2 神经、心脏 基因组的5'-UTR
和3'-UTR
浆细胞瘤 [27]
森林脑炎病毒 miR-124 6 神经 nsp3和nsp4之间 神经胶质瘤 [30]
麻疹病毒 miR-122、miR-7、miR-148a 3 神经、肝脏、胃肠 H和F的3'-UTR 胰腺癌 [33]
miR-124-3p、miR-125-5p、
miR-7-5p
3~6 神经 N、F、H和L的
3'-UTR
- [34]
miR-148a 3 胃肠 F的3'-UTR 胰腺癌 [35]
水泡性口炎病毒 Let-7 3 神经 M的3'-UTR 黑色素瘤 [40]
miR-125b 4 神经 L的3'-UTR 结直肠癌 [41]
腺病毒 miR-122 3 肝脏 E1A的3'-UTR - [44]
miR-148a、miR-216a 4~8 胰腺、肝脏 E1A的3'-UTR 胰腺癌 [45]
单纯疱疹病毒 miR-124-3p、miR-128-3p、
miR-137-3p、miR-204-5p、
miR-219a-5p、miR-1-3p、
miR-143-3p、miR-122-5p、
miR-126-3p、miR-217-5p
3 神经、心脏、肝脏、
胰腺
ICP4、ICP27、
UL8、ICP34.5的
3'-UTR
结直肠癌、
黑色素瘤
[48]
表3  miRNA去靶向的溶瘤病毒
病毒类型 miRNA 靶基因 作用效果 肿瘤模型 参考文献
腺病毒 miR-26b NF-κB 促进病毒复制 前列腺癌 [53]
miR-99b、miR-485 ELF4、MDM2、
KLF8
促进病毒复制 胰腺导管腺癌 [54]
miR-222海绵 miR-222 增强病毒复制
与细胞毒性
胰腺导管腺癌 [56]
水泡性口炎病毒 amiR-4 ARID1A 抑制干扰素通路,
提升溶瘤效果
胰腺导管腺癌、
黑色素瘤
[55]
表4  表达miRNA增强抗肿瘤作用的溶瘤病毒
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