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

Overview

Journal Front Oncol

Specialty Oncology

Date 2021 Nov 22

PMID 34804934

Authors

Guangcheng Bao

Jun Sun

Helin Zheng

Jingxin Hou

Jie Huang

Jie Wei

Yuanqiao Fu

Jiawen Qiu

Xuefeng Zou

Bin Xiang

Jinhua Cai

Affiliations

Soon will be listed here.

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.

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