Silencing microRNA‐221/222 cluster suppresses glioblastoma angiogenesis by suppressor of cytokine signaling‐3‐dependent JAK/STAT pathway

Autor: Chunhua Xu, Li-Min Xiao, Yue Liu, Li-Ke Chen, Er-Ming Zeng, Su-Yue Zheng, You-Ping Li, Dong-Hai Li
Rok vydání: 2019
Předmět:
0301 basic medicine
Carcinogenesis
Physiology
Angiogenesis
Clinical Biochemistry
Down-Regulation
Mice
Nude
Models
Biological
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Cell Movement
Cell Line
Tumor
Glioma
Human Umbilical Vein Endothelial Cells
medicine
Animals
Humans
Gene silencing
Neoplasm Invasiveness
Gene Silencing
SOCS3
STAT3
Cell Proliferation
Janus Kinases
Base Sequence
Neovascularization
Pathologic
biology
JAK-STAT signaling pathway
Cell Biology
medicine.disease
Up-Regulation
Gene Expression Regulation
Neoplastic
Vascular endothelial growth factor
MicroRNAs
STAT Transcription Factors
030104 developmental biology
chemistry
Suppressor of Cytokine Signaling 3 Protein
Multigene Family
030220 oncology & carcinogenesis
biology.protein
Cancer research
Glioblastoma
Janus kinase
Signal Transduction
Zdroj: Journal of Cellular Physiology. 234:22272-22284
ISSN: 1097-4652
0021-9541
Popis: Angiogenesis is a major pathologic characteristic of glioblastoma, which is one aggressive primary brain tumor. MicroRNA-221/222 (miR-221/222) cluster has been previously reported to function importantly in malignant glioma biological process. The current study aims at evaluating the effects of miR-221/222 cluster on angiogenesis of glioblastoma cells. Microarray data were analyzed to select glioblastoma-associated differentially expressed genes, and dual-luciferase reporter assay was performed to assess targeting correlation between miR-221/222 cluster and suppressor of cytokine signaling-3 (SOCS3). Subsequently, the expression patterns of miR-221 and miR-222 in glioblastoma cells were identified. miR-221 and miR-222 were overexpressed or silenced in glioblastoma cells to identify the effect of miR-221/222 cluster in cell invasion, migration, proliferation, and angiogenesis. To define downstream pathway of miR-221/222 cluster or SOCS3 in glioblastoma, levels of Janus kinase (JAK)/signal transducers and activators of transcription (STAT) pathway-related proteins were assessed. Additionally, the functions of miR-221/222 on glioblastoma cell angiogenesis were measured in vivo with microvessel density assayed. miR-221 and miR-222 were expressed at a high level and SOCS3 was at a low level in glioblastoma. Downregulation of the miR-221/222 cluster diminished the invasion, migration, proliferation, and angiogenesis with reduced protein levels of matrix metalloproteinase-2 (MMP-2), MMP-9, and vascular endothelial growth factor in glioblastoma cells. Also, silencing miR-221/222 cluster reduced p-JAK2/JAK2 and p-STAT3/STAT3. Consistently, the inhibitory role of silencing miR-221/222 cluster on tumorigenesis of glioblastoma cells was confirmed in vivo. Collectively, the inhibition of miR-221/222 cluster could attenuate the glioblastoma angiogenesis through inactivation of the JAK/STAT pathway by upregulating SOCS3.
Databáze: OpenAIRE
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