Glioblastoma (GBM) is the most frequent, aggressive and fatal tumor in the central nervous system, while PTEN signaling is frequently deregulated in human GBM. We previously reported the up-regulation of the carboxyl terminal of Hsp70-interacting protein (CHIP) in GBM, however, the causal link between its dysregulation and tumorigenesis has not been established. Using miRNA microarrays and quantitative RT-PCR (qRT-PCR), we found activation of CHIP leads to increased transcription of miR-92b. Further studies in T98G and LN229 cells showed overexpression of miR-92b elicited reduction of PTEN and efficiently rescued glioma development in CHIP knock-down cells. The core pathway, PI3K/Akt pathway, was then upregulated, which promoted GBM cell proliferation. Meanwhile, genetic ablation of miR-92b could restore PTEN expression and inhibit glioma growth. These data demonstrate that the CHIP/miR-92b/PTEN axis serves as a new mechanism underlying GBM tumorigenesis, providing potential new therapeutic targets.
Keywords: CHIP; Glioblastoma; PTEN; microRNA-92b; tumorigenesis.