Overexpression of HOXC6 promotes cell proliferation and migration via MAPK signaling and predicts a poor prognosis in glioblastoma

Background: Homeobox (HOX) genes encode transcription factors that are critical to morphogenesis and cell differentiation. Although the dysregulation of several HOX genes in glioblastoma (GBM) has been reported, little is known about HOXC6 expression in GBM. Therefore, in this study, we investigated the expression levels of the HOXC6 in GBM and explored the regulatory mechanism underlying the role of HOXC6 in GBM progression. Methods: The ONCOMINE and Oncolnc databases were used to predict the expression level of HOXC6 mRNA and its prognostic value in GBM. The expressions of HOXC6 mRNA in GBM tissues and adjacent brain tissues were detected using qRT-PCR and Western blot. Immunohistochemistry was performed to verify the HOXC6 protein expression in 107 GBM tissues. Kaplan-Meier and Cox analyses were performed to validate the correlation between HOXC6 expression and GBM prognosis. Lentivirus-mediated HOXC6 mRNA overexpression and interference system were established and transfected into U251 and U87 cell lines. CCK-8, colony formation, wound healing and transwell assay were utilized to evaluate the effects of HOXC6 on proliferation and migration of human GBM cells. Results: High expression of HOXC6 was observed in GBM tissues and GBM cells lines, and it correlated with a decreased overall survival and disease-free survival. Overexpression of HOXC6 promoted the GBM cell proliferation and migration, whereas depletion of HOXC6 reduced GBM cell proliferation and migration. Mechanistic study showed that upregulation of HOXC6 significantly increased the phosphorylation of Jun amino-terminal kinase, ERK and P38, as well as the expression of mitogen-activated protein kinase (MAPK) signaling-related genes, including c-myc, c-jun and p53. Inversely, silencing HOXC6 showed the opposite results. Conclusion: HOXC6 promoted proliferation and migration of GBM cells via the activation of MAPK pathway.