Knockdown ATG4C inhibits gliomas progression and promotes temozolomide chemosensitivity by suppressing autophagic flux

摘要: Gliomas are the most common primary tumors in central nervous system. Despite advances diagnosis and therapy, prognosis of glioma remains gloomy. Autophagy is a cellular catabolic process that degrades proteins damaged organelles, which implicated tumorigenesis tumor progression. related 4C cysteine peptidase (ATG4C) an autophagy regulator responsible for cleaving pro-LC3 delipidation LC3 II. This study was designed to investigate role ATG4C progression temozolomide (TMZ) chemosensitivity. The association between mRNA expression gliomas patients analyzed using TCGA datasets. proliferation, apoptosis, autophagy, TMZ chemosensitivity were investigated by silencing vivo. Ectopic xenograft nude mice model established effects on growth median overall survival (OS) time with higher significantly reduced (HR: 1.48, p = 9.91 × 10− 7). evidently increased rising grade (p = 2.97 × 10− 8). Knockdown suppressed cells proliferation inducing cell cycle arrest at G1 phase. depletion triggered apoptosis through ROS accumulation. Depletion TMZ-activated promoted sensitivity TMZ. Additionally, knockdown remarkably mice. potential prognostic predictor patient. Targeting may provide promising therapy strategies treatment.