miR-149 inhibits cell proliferation and enhances chemosensitivity by targeting CDC42 and BCL2 in neuroblastoma.

BACKGROUND

Neuroblastoma (NB) is one of most common childhood tumors with high mortality among children worldwide. microRNAs (miRNAs) have been reported to play essential roles in the pathogenesis and therapeutics of NB. However, the role of miR-149 and its mechanism remain poorly understood.

MAIN METHODS

The expression levels of miR-149, cell division cycle 42 (CDC42) and B-cell lymphoma 2 (BCL2) were measured in NB tissues or cells by quantitative real-time polymerase chain reaction or western blot. Cell proliferation was measured by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2--tetrazolium bromide (MTT) and colony formation assays. Cell apoptosis was detected by flow cytometry. Chemosensitivity of NB cells to doxorubicin (Dox) was analyzed by MTT assay. The interaction between miR-149 and CDC42 or BCL2 was explored by luciferase activity and RNA immunoprecipitation analyses.

RESULTS

Our data indicated that low expression of miR-149 was displayed in NB tissues and cells and associated with poor survival rate. Overexpression of miR-149 inhibited cell proliferation and colony formation but promoted cell apoptosis and chemosensitivity to Dox in NB cells. Moreover, CDC42 and BCL2 were targeted by miR-149. Additionally, CDC42 and BCL2 mRNA levels were elevated in NB tissues and cells and restoration of CDC42 or BCL2 reversed the regulatory effect of miR-149 on NB progression.

CONCLUSION

Our data suggested that miR-149 suppressed cell proliferation and improved Dox chemosensitivity by regulating CDC42 and BCL2 in NB, providing a novel avenue for treatment of NB.