Retraction: Specific interference of urokinase-type plasminogen activator receptor and matrix metalloproteinase-9 gene expression induced by double-stranded RNA results in decreased invasion, tumor growth, and angiogenesis in gliomas

Autor: Velidi H. Rao, Chrissa Sioka, Meena Gujrati, Christopher S. Gondi, Dzung H. Dinh, William C. Olivero, Sajani S. Lakka, Jasti S. Rao
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Male
Time Factors
Angiogenesis
Interference (genetic)
Biochemistry
Mice
Gene expression
Withdrawals/Retractions
Phosphorylation
RNA
Small Interfering
Receptor
Extracellular Signal-Regulated MAP Kinases
Promoter Regions
Genetic
Cell Line
Transformed
Neovascularization
Pathologic
Chemistry
Brain Neoplasms
Matrix metalloproteinase 9
Glioma
Immunohistochemistry
Drug Combinations
Matrix Metalloproteinase 9
Female
Proteoglycans
RNA Interference
Collagen
medicine.drug
MAP Kinase Signaling System
Genetic Vectors
Green Fluorescent Proteins
Down-Regulation
Mice
Nude
Receptors
Cell Surface
Transfection
Models
Biological
Gene Expression Regulation
Enzymologic
Receptors
Urokinase Plasminogen Activator
Cell Line
Tumor
medicine
Animals
Humans
Tumor growth
Neoplasm Invasiveness
Gene Silencing
Molecular Biology
Cell Proliferation
RNA
Double-Stranded
Urokinase
Models
Genetic
Cell Biology
Protein Structure
Tertiary
Cancer research
Nucleic Acid Conformation
Laminin
Glioblastoma
Plasminogen activator
Zdroj: J Biol Chem
Popis: We have previously demonstrated the effectiveness of adenovirus-mediated expression of antisense urokinase-type plasminogen activator receptor (uPAR) and matrix metalloproteinase-9 (MMP-9) in inhibiting tumor invasion in vitro and ex vivo. However, the therapeutic effect of the adenovirus-mediated antisense approach was shown to be transient and required potentially toxic, high viral doses. In contrast, RNA interference (RNAi)-mediated gene targeting may be superior to the traditional antisense approach, because the target mRNA is completely degraded and the molar ratio of siRNA required to degrade the target mRNA is very low. Here, we have examined the siRNA-mediated target RNA degradation of uPAR and MMP-9 in human glioma cell lines. Using RNAi directed toward uPAR and MMP-9, we achieved specific inhibition of uPAR and MMP-9. This bicistronic construct (pUM) inhibited the formation of capillary-like structures in both in vitro and in vivo models of angiogenesis. We demonstrated that blocking the expression of these genes results in significant inhibition of glioma tumor invasion in Matrigel and spheroid invasion assay models. RNAi for uPAR and MMP-9 inhibited cell proliferation, and significantly reduced the levels of phosphorylated forms of MAPK, ERK, and AKT signaling pathway molecules when compared with parental and empty vector/scrambled vector-transfected SNB19 cells. Furthermore, using RNAi to simultaneously target two proteases resulted in total regression of pre-established intracerebral tumor growth. Our results provide evidence that the use of hairpin siRNA expression vectors for uPAR and MMP-9 may provide an effective tool for cancer therapy.
Databáze: OpenAIRE
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