microRNA-124 inhibits migration and invasion by down-regulating ROCK1 in glioma.
BACKGROUND
The extraordinary invasive capability is a major cause of treatment failure and tumor recurrence in glioma, however, the molecular and cellular mechanisms governing glioma invasion remain poorly understood. Evidence in other cell systems has implicated the regulatory role of microRNA in cell motility and invasion, which promotes us to investigate the biological functions of miR-124 in glioma in this regard.


RESULTS
We have found that miR-124 is dramatically downregulated in clinical specimen of glioma and is negatively correlated with the tumor pathological grading in the current study. The cells transfected by miR-124 expression vector have demonstrated retarded cell mobility. Using a bioinformatics analysis approach, rho-associated coiled-coil containing protein kinase 1 (ROCK1), a well-known cell mobility-related gene, has been identified as the target of miR-124. A dual-luciferase reporter assay was used to confirm that miR-124 targeted directly the 3'UTR of ROCK1 gene and repressed the ROCK1 expression in U87MG human glioma cell line. Furthermore, experiments have shown that the decreased cell mobility was due to the actin cytoskeleton rearrangements and the reduced cell surface ruffle in U87MG glioma cells. These results are similar to the cellular responses of U87MG glioma cells to the treatment of Y-27632, an inhibitor of ROCK protein. Moreover, a constitutively active ROCK1 in miR-124 over-expressed glioma cells reversed the effects of miR-124. Our results revealed a novel mechanism that miR-124 inhibits glioma cells migration and invasion via ROCK1 downregulation.


CONCLUSIONS
These results suggest that miR-124 may function as anti-migration and anti-invasion influence in glioma and provides a potential approach for developing miR-124-based therapeutic strategies for malignant glioma therapy.
Key Laboratory of Medical Cell Biology, Ministry of Education, Department of Biochemistry and Molecular Biology, China Medical University, Shenyang, China.
Liwen
L
An
Yongjun
Y
Liu
Anhua
A
Wu
Yifu
Y
Guan
D020413:3' Untranslated Regions / Q000235:genetics; D008841:Actin Cytoskeleton / Q000378:metabolism; D001483:Base Sequence; D001932:Brain Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology* / Q000648:ultrastructure; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D022081:Cell Surface Extensions / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000201:enzymology / Q000235:genetics / Q000473:pathology* / Q000648:ultrastructure; D057809:HEK293 Cells; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D016133:Polymerase Chain Reaction; D054460:rho-Associated Kinases / Q000235:genetics* / Q000378:metabolism
D020413:3' Untranslated Regions; C509207:MIRN124 microRNA, human; D035683:MicroRNAs; C515851:ROCK1 protein, human; D054460:rho-Associated Kinases