The PABPC5/HCG15/ZNF331 Feedback Loop Regulates Vasculogenic Mimicry of Glioma via STAU1-Mediated mRNA Decay
| Autor: | Lianqi Shao, Jian Zheng, Xiaobai Liu, Yunhui Liu, Ping Wang, Yixue Xue, Fangkun Jing, Xuelei Ruan, Di Wang, Yang Yang, Shuyuan Shen, Jun Ma, Chunqing Yang |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cancer Research lcsh:RC254-282 Article 03 medical and health sciences 0302 clinical medicine Western blot PABPC5 Transcription (biology) glioma Glioma medicine Pharmacology (medical) Vasculogenic mimicry Transcription factor vasculogenic mimicry ZNF331 Tube formation Gene knockdown HCG15 medicine.diagnostic_test Chemistry Promoter lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens medicine.disease Cell biology 030104 developmental biology Oncology 030220 oncology & carcinogenesis Molecular Medicine |
| Zdroj: | Molecular Therapy Oncolytics Molecular Therapy: Oncolytics, Vol 17, Iss, Pp 216-231 (2020) |
| ISSN: | 2372-7705 |
| DOI: | 10.1016/j.omto.2020.03.017 |
| Popis: | 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. Graphical Abstract Glioma is the most common primary intracranial malignant tumor, and its main treatment methods are mainly surgical treatment combined with radiotherapy and chemotherapy and other comprehensive treatments after surgery, but after systematic treatment, the average median survival time of patients with glioma is only 12–18 months. Jing et al. demonstrate that PABPC5 increases the stability of HCG15. HCG15 promotes degradation of ZNF331 mRNA through the SMD pathway. ZNF331 binds to the promoter regions of LAMC2 and PABPC5 and inhibits their transcription, inhibiting formation of vasculogenic mimicry of glioma cells, which can affect the malignant biological behavior of glioma cells. |
| Databáze: | OpenAIRE |
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