Noninvasive Visualization of MicroRNA-16 in the Chemoresistance of Gastric Cancer Using a Dual Reporter Gene Imaging System
Open Access
- 17 April 2013
- journal article
- biology
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 8 (4), e61792
- https://doi.org/10.1371/journal.pone.0061792
Abstract
MicroRNAs (miRNAs) have been implicated to play a central role in the development of drug resistance in a variety of malignancies. However, many studies were conducted at the in vitro level and could not provide the in vivo information on the functions of miRNAs in the anticancer drug resistance. Here, we introduced a dual reporter gene imaging system for noninvasively monitoring the kinetic expression of miRNA-16 during chemoresistance in gastric cancer both in vitro and in vivo. Human sodium iodide symporter (hNIS) and firefly luciferase (Fluc) genes were linked to form hNIS/Fluc double fusion reporter gene and then generate human gastric cancer cell line NF-3xmir16 and its multidrug resistance cell line NF-3xmir16/VCR. Radioiodide uptake and Fluc luminescence signals in vitro correlated well with viable cell numbers. The luciferase activities and radioiodide uptake in NF-3xmir16 cells were remarkably repressed by exogenous or endogenous miRNA-16. The NF-3xmir16/VCR cells showed a significant increase of 131I uptake and luminescence intensity compared to NF-3xmir16 cells. The radioactivity from in vivo 99mTc-pertechnetate imaging and the intensity from bioluminescence imaging were also increased in NF-3xmir16/VCR compared with that in NF-3xmir16 tumor xenografts. Furthermore, using this reporter gene system, we found that etoposide (VP-16) and 5-fluorouracil (5-FU) activated miRNA-16 expression in vitro and in vivo, and the upregulation of miRNA-16 is p38MAPK dependent but NF-κB independent. This dual imaging reporter gene may be served as a novel tool for in vivo imaging of microRNAs in the chemoresistance of cancers, as well as for early detection and diagnosis in clinic.This publication has 25 references indexed in Scilit:
- Dual optical biosensors for imaging microRNA-1 during myogenesisBiomaterials, 2012
- A reverse complementary multimodal imaging system to visualize microRNA9-involved neurogenesis using peptide targeting transferrin receptor-conjugated magnetic fluorescence nanoparticlesBiomaterials, 2012
- Molecular imaging of microRNAsEuropean Journal of Nuclear Medicine and Molecular Imaging, 2011
- Implication of microRNAs in drug resistance for designing novel cancer therapyDrug Resistance Updates, 2010
- Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008International Journal of Cancer, 2010
- Molecular-Genetic Imaging Based on Reporter Gene ExpressionJournal of Nuclear Medicine, 2008
- miR‐15b and miR‐16 modulate multidrug resistance by targeting BCL2 in human gastric cancer cellsInternational Journal of Cancer, 2008
- Chemotherapy of advanced gastric cancerCancer Treatment Reviews, 2007
- MicroRNAs: Genomics, Biogenesis, Mechanism, and FunctionCell, 2004
- Molecular imaging in living subjects: seeing fundamental biological processes in a new lightGenes & Development, 2003