Loss of TXNDC12 Induces Oxidative Stress-mediated Autophagy in Glioblastoma Cell Lines

Redox homeostasis in glioblastoma cells is very important, but how it is maintained is still not well understood. Herein, we identified thioredoxin domain-containing protein 12 (TXNDC12) as a therapeutic target candidate which significantly maintained redox homeostasis in GBM cells. Overexpression of TXNDC12 was associated with increased tumor grade and poor prognosis in patients with glioma (P < 0.001), according to the analysis of expression data from the public database Cancer Genome Atlas. TXNDC12 protein levels were significantly elevated in glioblastoma compared to non-tumor brain tissue samples by immunohistochemistry and western blot analysis. Knockdown of TXNDC12 inhibited the proliferation of U251 and A172 in vitro . On day 21 post-implantation, tumor growth inhibition was 70% in A172 with stable expression of TXNDC12 shRNA in vivo (P < 0.001). Kaplan-Meier analysis of survival data showed that the overall survival of tumor-bearing animals increased from 20.3 days (control) to 28.7 days (knockout, P < 0.05). These data suggest that TXNDC12 is a key mediator in redox homeostasis both in vivo and in vitro . Thus, TXNDC12 is a potential treatment target of GBM.