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 MEOX2 also hampered the epithelial-mesenchymal transition (EMT), focal adhesion formation, and
F-actin assembly. Overexpression of MEOX2 exhibited opposite effects. Importantly,
RNA-sequencing, ChIP-qPCR 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 MEOX2-CTSS axis might be a promising alternative for the treatment of
glioma.