Visualization of microRNA-21 Dynamics in Neuroblastoma Using Magnetic Resonance Imaging Based on a microRNA-21-Responsive Reporter Gene
BackgroundMicroRNAs (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 a...
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Frontiers Media S.A.
2021
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oai:doaj.org-article:9ac416193fb945709f630bbf55739e162021-11-05T12:03:18ZVisualization of microRNA-21 Dynamics in Neuroblastoma Using Magnetic Resonance Imaging Based on a microRNA-21-Responsive Reporter Gene2234-943X10.3389/fonc.2021.747305https://doaj.org/article/9ac416193fb945709f630bbf55739e162021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fonc.2021.747305/fullhttps://doaj.org/toc/2234-943XBackgroundMicroRNAs (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.MethodsThe 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 in vitro and in vivo.ResultsIn 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 in vitro and in vivo.ConclusionMRI 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.Guangcheng BaoGuangcheng BaoGuangcheng BaoGuangcheng BaoJun SunJun SunJun SunJun SunHelin ZhengJingxin HouJie HuangJie HuangJie HuangJie HuangJie WeiJie WeiJie WeiJie WeiYuanqiao FuYuanqiao FuYuanqiao FuYuanqiao FuJiawen QiuJiawen QiuJiawen QiuJiawen QiuXuefeng ZouBin XiangJinhua CaiJinhua CaiJinhua CaiJinhua CaiFrontiers Media S.A.articlemicroRNA-21reporter geneferritin heavy chainmagnetic resonance imagingneuroblastomaNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENFrontiers in Oncology, Vol 11 (2021) |
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microRNA-21 reporter gene ferritin heavy chain magnetic resonance imaging neuroblastoma Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 |
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microRNA-21 reporter gene ferritin heavy chain magnetic resonance imaging neuroblastoma Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Guangcheng Bao Guangcheng Bao Guangcheng Bao Guangcheng Bao Jun Sun Jun Sun Jun Sun Jun Sun Helin Zheng Jingxin Hou Jie Huang Jie Huang Jie Huang Jie Huang Jie Wei Jie Wei Jie Wei Jie Wei Yuanqiao Fu Yuanqiao Fu Yuanqiao Fu Yuanqiao Fu Jiawen Qiu Jiawen Qiu Jiawen Qiu Jiawen Qiu Xuefeng Zou Bin Xiang Jinhua Cai Jinhua Cai Jinhua Cai Jinhua Cai Visualization of microRNA-21 Dynamics in Neuroblastoma Using Magnetic Resonance Imaging Based on a microRNA-21-Responsive Reporter Gene |
| description |
BackgroundMicroRNAs (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.MethodsThe 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 in vitro and in vivo.ResultsIn 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 in vitro and in vivo.ConclusionMRI 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. |
| format |
article |
| author |
Guangcheng Bao Guangcheng Bao Guangcheng Bao Guangcheng Bao Jun Sun Jun Sun Jun Sun Jun Sun Helin Zheng Jingxin Hou Jie Huang Jie Huang Jie Huang Jie Huang Jie Wei Jie Wei Jie Wei Jie Wei Yuanqiao Fu Yuanqiao Fu Yuanqiao Fu Yuanqiao Fu Jiawen Qiu Jiawen Qiu Jiawen Qiu Jiawen Qiu Xuefeng Zou Bin Xiang Jinhua Cai Jinhua Cai Jinhua Cai Jinhua Cai |
| author_facet |
Guangcheng Bao Guangcheng Bao Guangcheng Bao Guangcheng Bao Jun Sun Jun Sun Jun Sun Jun Sun Helin Zheng Jingxin Hou Jie Huang Jie Huang Jie Huang Jie Huang Jie Wei Jie Wei Jie Wei Jie Wei Yuanqiao Fu Yuanqiao Fu Yuanqiao Fu Yuanqiao Fu Jiawen Qiu Jiawen Qiu Jiawen Qiu Jiawen Qiu Xuefeng Zou Bin Xiang Jinhua Cai Jinhua Cai Jinhua Cai Jinhua Cai |
| author_sort |
Guangcheng Bao |
| title |
Visualization of microRNA-21 Dynamics in Neuroblastoma Using Magnetic Resonance Imaging Based on a microRNA-21-Responsive Reporter Gene |
| title_short |
Visualization of microRNA-21 Dynamics in Neuroblastoma Using Magnetic Resonance Imaging Based on a microRNA-21-Responsive Reporter Gene |
| title_full |
Visualization of microRNA-21 Dynamics in Neuroblastoma Using Magnetic Resonance Imaging Based on a microRNA-21-Responsive Reporter Gene |
| title_fullStr |
Visualization of microRNA-21 Dynamics in Neuroblastoma Using Magnetic Resonance Imaging Based on a microRNA-21-Responsive Reporter Gene |
| title_full_unstemmed |
Visualization of microRNA-21 Dynamics in Neuroblastoma Using Magnetic Resonance Imaging Based on a microRNA-21-Responsive Reporter Gene |
| title_sort |
visualization of microrna-21 dynamics in neuroblastoma using magnetic resonance imaging based on a microrna-21-responsive reporter gene |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/9ac416193fb945709f630bbf55739e16 |
| work_keys_str_mv |
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