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核心技术专利：CN118964589B侵权必究
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基于微小RNA-21响应报告基因，利用磁共振成像技术对神经母细胞瘤中微小RNA-21动态变化进行可视化研究。

Visualization of microRNA-21 Dynamics in Neuroblastoma Using Magnetic Resonance Imaging Based on a microRNA-21-Responsive Reporter Gene.

作者信息

Bao Guangcheng, Sun Jun, Zheng Helin, Hou Jingxin, Huang Jie, Wei Jie, Fu Yuanqiao, Qiu Jiawen, Zou Xuefeng, Xiang Bin, Cai Jinhua

机构信息

Department of Radiology, Children's Hospital of Chongqing Medical University, Chongqing, China.

Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China.

出版信息

Front Oncol. 2021 Nov 5;11:747305. doi: 10.3389/fonc.2021.747305. eCollection 2021.

DOI:10.3389/fonc.2021.747305
PMID:34804934
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8602822/
Abstract

BACKGROUND: MicroRNAs (miRs) have been shown to be closely associated with the occurrence and development of tumors and to have potential as diagnostic and therapeutic targets. The detection of miRs by noninvasive imaging technology is crucial for deeply understanding their biological functions. Our aim was to develop a novel miR-21-responsive gene reporter system for magnetic resonance imaging (MRI) visualization of the miR-21 dynamics in neuroblastoma. METHODS: The reporter gene ferritin heavy chain (FTH1) was modified by the addition of 3 copies of the sequence completely complementary to miR-21 (3xC_miR-21) to its 3'-untranslated region (3' UTR) and transduced into SK-N-SH cells to obtain SK-N-SH/FTH1-3xC_miR-21 cells. Then, the antagomiR-21 was delivered into cells by graphene oxide functionalized with polyethylene glycol and dendrimer. Before and after antagomiR-21 delivery, FTH1 expression, MRI contrast and intracellular iron uptake were assayed and . RESULTS: In the SK-N-SH/FTH1-3xC_miR-21 cells, FTH1 expression was in an "off" state due to the combination of intratumoral miR-21 with the 3' UTR of the reporter gene. AntagomiR-21 delivered into the cells bound to miR-21 and thereby released it from the 3' UTR of the reporter gene, thus "switching on" FTH1 expression in a dose-dependent manner. This phenomenon resulted in intracellular iron accumulation and allowed MRI detection and . CONCLUSION: MRI based on the miR-21-responsive gene reporter may be a potential method for visualization of the endogenous miR-21 activity in neuroblastoma and its response to gene therapy.

摘要

背景：微小RNA（miR）已被证明与肿瘤的发生发展密切相关，并具有作为诊断和治疗靶点的潜力。通过非侵入性成像技术检测miR对于深入了解其生物学功能至关重要。我们的目的是开发一种新型的miR-21响应基因报告系统，用于磁共振成像（MRI）可视化神经母细胞瘤中miR-21的动态变化。 方法：将报告基因铁蛋白重链（FTH1）的3'非翻译区（3'UTR）添加3个与miR-21完全互补的序列拷贝（3xC_miR-21）进行修饰，然后转导至SK-N-SH细胞中，获得SK-N-SH/FTH1-3xC_miR-21细胞。随后，通过聚乙二醇和树枝状大分子功能化的氧化石墨烯将抗miR-21递送至细胞中。在递送抗miR-21前后，检测FTH1表达、MRI对比度和细胞内铁摄取情况。 结果：在SK-N-SH/FTH1-3xC_miR-21细胞中，由于肿瘤内miR-21与报告基因的3'UTR结合，FTH1表达处于“关闭”状态。递送至细胞中的抗miR-21与miR-21结合，从而将其从报告基因的3'UTR释放，进而以剂量依赖方式“开启”FTH1表达。这种现象导致细胞内铁积累，并实现MRI检测。 结论：基于miR-21响应基因报告的MRI可能是一种可视化神经母细胞瘤内源性miR-21活性及其对基因治疗反应的潜在方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cbc9/8602822/feebf0a2c796/fonc-11-747305-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cbc9/8602822/8ba8d01dbc62/fonc-11-747305-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cbc9/8602822/c5d50079c206/fonc-11-747305-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cbc9/8602822/f0386be248a7/fonc-11-747305-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cbc9/8602822/20a9372f7a4c/fonc-11-747305-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cbc9/8602822/686888da58fb/fonc-11-747305-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cbc9/8602822/feebf0a2c796/fonc-11-747305-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cbc9/8602822/8ba8d01dbc62/fonc-11-747305-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cbc9/8602822/c5d50079c206/fonc-11-747305-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cbc9/8602822/f0386be248a7/fonc-11-747305-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cbc9/8602822/20a9372f7a4c/fonc-11-747305-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cbc9/8602822/686888da58fb/fonc-11-747305-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cbc9/8602822/feebf0a2c796/fonc-11-747305-g006.jpg

相似文献

[1]
Visualization of microRNA-21 Dynamics in Neuroblastoma Using Magnetic Resonance Imaging Based on a microRNA-21-Responsive Reporter Gene.

Front Oncol. 2021-11-5

[2]
In Vivo magnetic resonance imaging of xenografted tumors using FTH1 reporter gene expression controlled by a tet-on switch.

Oncotarget. 2016-11-29

[3]
MRI detection of the malignant transformation of stem cells through reporter gene expression driven by a tumor-specific promoter.

Stem Cell Res Ther. 2021-5-12

[4]
Cellular magnetic resonance imaging contrast generated by the ferritin heavy chain genetic reporter under the control of a Tet-On switch.

Stem Cell Res Ther. 2015-10-31

[5]
Imaging Dendrimer-Grafted Graphene Oxide Mediated Anti-miR-21 Delivery With an Activatable Luciferase Reporter.

ACS Appl Mater Interfaces. 2016-4-1

[6]
microRNA-9 targets matrix metalloproteinase 14 to inhibit invasion, metastasis, and angiogenesis of neuroblastoma cells.

Mol Cancer Ther. 2012-5-7

[7]
Neural Differentiation of Bone Marrow Mesenchymal Stem Cells Carrying the FTH1 Reporter Gene and Detection with MRI.

Biomed Res Int. 2018-6-26

[8]
Efficiency of ferritin as an MRI reporter gene in NPC cells is enhanced by iron supplementation.

J Biomed Biotechnol. 2012

[9]
MRI Tracking of SPIO- and -Labeled Bone Marrow Mesenchymal Stromal Cell Transplantation for Treatment of Stroke.

Contrast Media Mol Imaging. 2019-8-29

[10]
MicroRNA-145 inhibits the growth, invasion, metastasis and angiogenesis of neuroblastoma cells through targeting hypoxia-inducible factor 2 alpha.

Oncogene. 2012-12-10

本文引用的文献

[1]
MRI detection of the malignant transformation of stem cells through reporter gene expression driven by a tumor-specific promoter.

Stem Cell Res Ther. 2021-5-12

[2]
The interaction between ferroptosis and lipid metabolism in cancer.

Signal Transduct Target Ther. 2020-6-30

[3]
Graphene oxide-based nanomaterial interaction with human breast cancer cells.

J Biomed Mater Res A. 2020-4

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Glycyrrhetinic acid-modified graphene oxide mediated siRNA delivery for enhanced liver-cancer targeting therapy.

Eur J Pharm Sci. 2019-8-22

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Anti-miRNA Oligonucleotide Therapy for Chondrosarcoma.

Mol Cancer Ther. 2019-7-24

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Neural Differentiation of Bone Marrow Mesenchymal Stem Cells Carrying the FTH1 Reporter Gene and Detection with MRI.

Biomed Res Int. 2018-6-26

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J Allergy Clin Immunol. 2017-10-23

[8]
T2-Weighted Magnetic Resonance Imaging of Hepatic Tumor Guided by SPIO-Loaded Nanostructured Lipid Carriers and Ferritin Reporter Genes.

ACS Appl Mater Interfaces. 2017-10-4

[9]
Ultrasmall graphene oxide based T MRI contrast agent for in vitro and in vivo labeling of human mesenchymal stem cells.

Nanomedicine. 2017-5-26

[10]
In Vivo Molecular Bioluminescence Imaging: New Tools and Applications.

Trends Biotechnol. 2017-5-10

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