Cardiotrophin-like cytokine factor 1 regulated by Sry-related HMG-box transcription factor 9 promotes malignant behavior and immune evasion of glioblastoma multiforme.

Abstract

Cardiotrophin-like cytokine factor 1 (CLCF1) is an unfavorable factor for the prognosis of patients with glioblastoma multiforme (GBM). This research explored the functions of CLCF1 in GBM progression and the underlying regulatory mechanisms. Reverse transcription-quantitative PCR (RT-qPCR) and Western blot were used to detect the mRNA and protein levels of targeted molecules. The abilities of GBM cell lines to proliferate, migrate, and invade and undergo apoptosis and angiogenesis were analyzed by colony formation, transwell, TUNEL, and tube formation assays, respectively. Interaction between CLCF1 and SRY-box transcription factor 9 (SOX9) was verified by chromatin immunoprecipitation (ChIP)-qPCR and dual-luciferase reporter assays. The results showed that CLCF1 was upregulated in GBM. Silencing of CLCF1 suppressed the malignant phenotypes of GBM cells in vitro and the development of GBM in a xenograft tumor model. Silencing CLCF1 also reduced programmed cell death 1 ligand 1 (PD-L1) expression in GBM cells and prolonged the longevity of CD8-positive T cells in vitro. SRY-box transcription factor 9 was highly expressed in GBM and this activated CLCF1 expression as one of its transcription factors to further enhance GBM development. Thus, CLCF1 regulated by SOX9 can enhance the development and immune evasion of GBM.