The PABPC5/HCG15/ZNF331 Feedback Loop Regulates Vasculogenic Mimicry of Glioma via STAU1-Mediated mRNA Decay

Mol Ther Oncolytics. 2020 Mar 30;17:216-231. doi: 10.1016/j.omto.2020.03.017. eCollection 2020 Jun 26.

Abstract

Glioma is the most common primary malignancy in the brain, and vasculogenic mimicry (VM) is one of the blood supply methods. Here we investigated the possibility that lncRNAs regulate the stability of transcription factors through the SMD pathway, which affects proliferation, migration, invasion, and the ability to form VMs in glioma. Expression of PABPC5, HCG15, and ZNF331 was detected by real-time qPCR or western blot in glioma. Cell Counting Kit-8, Transwell assays, and in vitro VM tube formation were used to investigate PABPC5, HCG15, and ZNF331 function in cell proliferation, migration, invasion, and VM, respectively. ChIP assays were used to ascertain the interaction betweenZNF331 and LAMC2 or PABPC5. PABPC5 and HCG15 were highly expressed in glioma cells. ZNF331 was lowly expressed. PABPC5 bound HCG15 to increase its stability. Knockdown HCG15 reduced the degradation of ZNF331 mRNA by the SMD pathway. ZNF331 inhibited transcription through binding to the promoter region of LAMC2 and PABPC5 and inhibited the ability to form VMs in glioma cells. The PABPC5/HCG15/ZNF331 feedback loop plays an important role in regulating VM formation in glioma and provides new targets for glioma treatment.

Keywords: HCG15; PABPC5; ZNF331; glioma; vasculogenic mimicry.