Cancer-testis Specific Gene OIP5: A Downstream Gene of E2F1 that Promotes Tumorigenesis and Metastasis in Glioblastoma by Stabilizing E2F1 Signalling

Abstract

Background

The cancer-testis specific gene Opa interacting protein 5 (OIP5) is a testis-specific gene that is reactivated in many human cancers, but its functions in glioblastoma remain unclear. Here, we assessed the significance of OIP5 in the tumorigenesis and metastasis of glioblastoma for the first time.

Methods

An immunohistochemistry assay was performed to detect OIP5 expression changes in glioblastoma patients. Overall survival analysis was performed to evaluate the prognostic significance of OIP5. Growth curve, colony formation and transwell assays were used to analyse cell proliferation and metastasis. Tumorigenicity potential was investigated in orthotopic tumour models, and immunoprecipitation, chromatin immunoprecipitation, and luciferase assays were employed to explore the mechanisms underlying the activation of OIP5 expression by E2F transcription factor 1 (E2F1) to stabilize and maintain E2F1 signalling.

Results

OIP5 was found to be upregulated in glioblastoma patients and to impair patient survival, and the increased expression of OIP5 was positively correlated with tumour stage. Compared with shGFP cells, cells in which OIP5 was knocked down exhibited significantly reduced proliferation, metastasis, colony formation and tumorigenicity abilities, whereas OIP5 recovery enhanced these abilities. OIP5 was highly correlated with cell cycle progression but had no obvious effects on apoptosis. Notably, we demonstrated a feed-back loop in which E2F1 activates the expression of OIP5 to stabilize and maintain E2F1 signalling, promote the E2F1-regulated gene expression that is required for aggressive tumour biology.

Conclusions

Collectively, our findings demonstrate that OIP5 promotes glioblastoma progression and metastasis, suggesting that OIP5 is a potential target for anti-cancer therapy.