MEOX2-mediated regulation of Cathepsin S promotes cell proliferation and motility in glioma.

Nuclear transcription factor Mesenchyme Homeobox 2 (MEOX2) is a homeobox gene that is originally discovered to suppress the growth of vascular smooth muscle and endothelial cells. However, whether or not it is connected to cancer is yet unknown. Here, we report that MEOX2 functions as a tumor-initiating element in glioma. Bioinformatic analyses of public databases and investigation of MEOX2 expression in patients with glioma demonstrated that MEOX2 was abundant at both mRNA and protein levels in glioma. MEOX2 expression was shown to be inversely linked with the prognosis of glioma patients. MEOX2 inhibition changed the morphology of glioma cells, inhibited cell proliferation and motility, whereas had no effect on cell apoptosis. Besides, silencing of MEOX2 also hampered the epithelial-mesenchymal transition (EMT), focal adhesion maturation, and F-actin assembly. Overexpression of MEOX2 exhibited opposite effects. Importantly, RNA-seq, ChIP assay, and luciferase reporter assay revealed Cathepsin S (CTSS) as a novel transcriptional target of MEOX2 in glioma cells. Consistently, MEOX2 causes glioma tumor development in mice and greatly lowers the survival period of tumor-bearing mice. Our findings indicate that MEOX2 promotes tumorigenesis and progression of glioma partially through the regulation of CTSS. Targeting the MEOX2-CTSS axis might be a promising alternative for the treatment of glioma. Overall design: To test the effect of suppression of MEOX2 on the gene expression, SNB19 cells were transfected with MEOX2 Scramble siRNA (Control) or MEOX2 siRNA. MEOX2-knockdown SNB19 cells were compared to control cells. To test the effect of activation of MEOX2 on the gene expression, U87 cells were transfected with MEOX2 empty vector (EV) or MEOX2 overexpression lentivirals. MEOX2-overexpression U87 cells were compared to control cells.