VSIG4 Silencing Inhibits Glioblastoma Growth by Regulating the JAK2/STAT3 Pathway

Congying Zheng,* Chengliang Mao,* Kai Tang, Hang Shu Department of Neurosurgery, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou City, Guangdong Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hang Shu, Department of Neurosurgery, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, No. 106, Zhongshan Er Road, Guangzhou City, Guangdong Province, 510080, People’s Republic of China, Tel +86- 13902204543, Email zhengcongying@gdph.org.cnBackground: Glioblastoma (GBM) is the most common malignant primary brain tumour in adults. VSIG4 has been identified to be associated with GBM. We aimed to determine the downstream regulatory mechanisms of VSIG4 in GBM.Methods: Differential expression of VSIG4 was analysed using GEPIA. The expression of VSIG4 was assessed by RT-qPCR and its downstream genes were screened by transcriptome sequencing. The expression of pyroptosis-related proteins and the JAK2/STAT3 pathway was measured by Western blotting. GBM cell viability, migration, and invasion were detected using CCK-8, scratch, and Transwell assays. The levels of pyroptosis-related factors were measured using ELISA. The effect of VSIG4 on GBM tumour growth in vivo was explored by constructing a xenograft tumour model.Results: VSIG4 expression was upregulated in GBM. Functionally, silencing of VSIG4 inhibited proliferation, invasion, and migration of U251 and LN229 cells, and promoted pyroptosis. Mechanically, transcriptome sequencing revealed that the JAK2/STAT3 pathway might be a downstream regulator of VSIG4. Further studies proved that silencing of VSIG4 enhanced the expression of p-JAK2 and p-STAT3, and the JAK2/STAT3 pathway inhibitor relieved the suppression of VSIG4 silencing on GBM cell viability, invasion, and migration. Furthermore, in vivo experiments further validated that knockdown of VSIG4 inhibited the growth of GBM tumors.Conclusion: In GBM, silencing VSIG4 promoted pyroptosis and inhibited tumor progression by regulating the JAK2/STAT3 signaling pathway.Keywords: glioblastoma, VSIG4, JAK2/STAT3 pathway, pyroptosis