Medulloblastoma malignant biological behaviors are associated with HOTAIR/miR-483-3p/CDK4 axis.

Background: Medulloblastoma is the most common malignant brain tumor in children. Although the 5-year survival rate is high, patients with relapsed medulloblastoma have a guarded prognosis. HOX transcript antisense RNA (HOTAIR) has been proved to be related to the metastasis of various tumors. Therefore, the molecular mechanism of HOTAIR in medulloblastoma cells was investigated in this study.

Methods: HOTAIR was stably silenced in medulloblastoma cells (Daoy and D341). Cell proliferation and apoptosis were detected by 5'-Bromo-2'-deoxyuridine (BrdU) staining, Hoechst 33342 staining, immunohistochemical (IHC), Terminal-deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) and flow cytometry, respectively. The targeted relationship between HOTAIR/Cyclin-dependent kinase 4 (CDK4) and miR-483-3p were predicted by bioinformatics and confirmed by luciferase reporter assay. Balb/C nude mice were inoculated with shRNA-HOTAIR transfected Daoy cells.

Results: We found that the down-regulation of HOTAIR inhibited proliferation and induced apoptosis. Sh-RNA-HOTAIR also inhibited the expression of CKD4. The CDK4 dependent increase of cell proliferation and decrease of cell apoptosis were reversed by shRNA-HOTAIR. Finally, a xenograft model of medulloblastoma in nude mice was built, and the effect of shRNA-HOTAIR on the growth of tumors was analyzed by RT-PCR, immunofluorescence staining, and TUNEL staining. The data suggested interference of HOTAIR inhibited the growth, tumor weight, cell proliferation, and promoted cell apoptosis.

Conclusions: Our study altogether demonstrated HOTAIR influence cell proliferation and apoptosis by regulation of miR-483-3p and CDK4 in medulloblastoma cells. HOTAIR can be used as a candidate for potential applications in the treatment of medulloblastoma.