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MicroRNA-106a suppresses proliferation, migration, and invasion of bladder cancer cells by modulating MAPK signaling, cell cycle regulators, and Ets-1-mediated MMP-2 expression.
- Source :
-
Oncology reports [Oncol Rep] 2016 Oct; Vol. 36 (4), pp. 2421-9. Date of Electronic Publication: 2016 Aug 11. - Publication Year :
- 2016
-
Abstract
- Despite the clinical significance of tumorigenesis, little is known about the cellular signaling networks of microRNAs (miRs). Here we report a new finding that mir‑106a regulates the proliferation, migration, and invasion of bladder cancer cells. Basal expression levels of mir‑106a were significantly lower in bladder cancer cells than in normal urothelial cells. Overexpression of mir‑106a suppressed the proliferation of bladder cancer cell line EJ. Transient transfection of mir‑106a into EJ cells led to downregulation of ERK phosphorylation and upregulation of p38 and JNK phosphorylation over their levels in the control. Flow cytometry analysis revealed that mir‑106a-transfected cells accumulated in the G1-phase of the cell cycle, and cyclin D1 and CDK6 were significantly downregulated. This G1-phase cell cycle arrest was due in part to the upregulation of p21CIP1/WAF1. In addition, mir‑106a overexpression blocked the wound-healing migration and invasion of EJ cells. Furthermore, mir‑106a transfection resulted in decreased expression of MMP-2 and diminished binding activity of transcription factor Ets-1 in EJ cells. Collectively, we report the novel mir‑106a-mediated molecular signaling networks that regulate the proliferation, migration, and invasion of bladder cancer cells, suggesting that mir‑106a may be a therapeutic target for treating advanced bladder tumors.
- Subjects :
- Cell Cycle Proteins biosynthesis
Cell Cycle Proteins genetics
Cell Line, Tumor
Cell Movement genetics
Cell Proliferation genetics
Cyclin-Dependent Kinase Inhibitor p21 biosynthesis
Gene Expression Regulation, Neoplastic
Humans
Matrix Metalloproteinase 2 biosynthesis
MicroRNAs biosynthesis
Neoplasm Invasiveness genetics
Phosphorylation
Proto-Oncogene Protein c-ets-1 biosynthesis
Signal Transduction
Urinary Bladder Neoplasms pathology
Matrix Metalloproteinase 2 genetics
MicroRNAs genetics
Proto-Oncogene Protein c-ets-1 genetics
Urinary Bladder Neoplasms genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1791-2431
- Volume :
- 36
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Oncology reports
- Publication Type :
- Academic Journal
- Accession number :
- 27513725
- Full Text :
- https://doi.org/10.3892/or.2016.5015