c-Fos/microRNA-18a feedback loop modulates the tumor growth via HMBOX1 in human gliomas

Glioma is one of the most aggressive and lethal human cancers in central nervous system (CNS). Recent studies have identified many dysregulated microRNAs (miRNA, miR) in human glioma, which are a class of small non-coding RNA molecules. Increasing data have shown that miR-18a plays significant roles in several tumors. However, its effects on glioma are unclear. In this study, we found the elevated expression of c-Fos and miR-18a in tissues of human glioma patients and glioma cells. Then the miR-18a inhibitor or c-Fos siRNA were transfected into glioma cells line H4 to determine their effects on H4 cells. MTT assay showed that both miR-18a inhibitor and si-c-Fos suppressed the H4 cell proliferation. Transwell assay showed the reduced cell migration by miR-18a inhibitor and si-c-Fos in H4 cells. The increased level of H4 cells apoptosis by miR-18a inhibitor and si-c-Fos was also determined. Moreover, knockout of c-Fos decreased the miR-18a level, while miR-18a inhibitor reduced the c-Fos level in H4 cells. Added with the results of ChIP assay, this report showed a positive feedback between c-Fos and miR-18a. Finally, luciferase assay showed that HMBOX1 was directly targeted by miR-18a in H4 cells, and the HMBOX1 siRNA reversed the effects of miR-18a inhibitor on cell proliferation, migration and apoptosis of H4 cells. In conclusion, our study determine that c-Fos/miR-18a feedback loop promotes the tumor growth of gliomas by HMBOX1, providing important clues for understanding the key roles of transcription factor mediated mRNA-miRNA functional network in the regulation of gliomas.