CISD2 promotes the proliferation of glioma cells via suppressing beclin-1-mediated autophagy and is targeted by microRNA-449a

摘要

CDGSH iron sulfur domain 2 (CISD2) has been found to be important in carcinogenesis. However, the role of CISD2 in glioma remains to be elucidated. The present study aimed to investigate the role of CISD2 in glioma using the reverse transcription-quantitative polymerase chain reaction, western blotting, co-immunoprecipitation assay, immunofluorescence staining and other methods. The results demonstrated that the mRNA and protein levels of CISD2 were found to be upregulated in glioma tissues, compared with the levels in matched normal tissues. Clinical data analysis showed that the level of CISD2 was negatively correlated with the survival rates of patients with glioma. In addition, high levels of CISD2 were associated with advanced clinical stage, relapse, vascular invasion and increased tumor size. The inhibition of CISD2 suppressed the proliferation and survival of glioma cells in vitro and in vivo. Mechanistically, it was found that small interfering RNA-induced knock down of CISD2 inhibited the proliferation of glioma cells through activating beclin-1-mediated autophagy. The results also revealed that CISD2 was a target of microRNA (miR)-449a. Together, the results of the present study demonstrated that CISD2 was increased in glioma samples and was associated with poor prognosis and aggressive tumor behavior. The miR-449a/CISD2/beclin-1-mediated autophagy regulatory network contributed to the proliferation of glioma cells. Targeting this pathway may be a promising strategy for glioma therapy.