HOXC6 Effects Glioma Progression By The Wnt Signaling Pathway

Glioma is one of the most common malignant brain tumors,accounting for about 80% of primary malignant central nervous system(CNS)tumors.It has the characteristics of high morbidity,high recurrence,and high mortality.Despite the rapid development of medical technology,including surgical resection,supplemented by radiotherapy and chemotherapy,the treatment effect of glioma is not good.The 1-year and 5-year survival rates of adult high-grade glioma are about30% and 13%,respectively.The median survival time of degenerative glioma and glioblastoma is about 2-3 years and 1 year,respectively.Malignant tumors of the central nervous system represented by gliomas have caused huge social and economic burdens and family pressures.Therefore,it is particularly important to develop new glioma treatment drugs and design more effective treatment strategies.The protein encoded by the homeobox C6(Homeobox C6,HOXC6)gene is a very important transcriptional regulator in biological cells,which regulates cell proliferation,differentiation,apoptosis,angiogenesis,receptor signal transduction,embryonic development,tissue and organ formation Play an important role in the city.This has been confirmed in more and more cancer studies in recent years.HOX gene changes have been found in malignant tumors such as gastric cancer,breast cancer,prostate cancer,lung cancer and leukemia.HOX gene is a carcinogenic transcription factor.Participate in a variety of regulatory pathways related to the malignant progression of tumors.Recent studies have shown that changes in the expression of HOXC6 can affect the invasion ability of glioma U-118 cells,but the function and mechanism of HOXC6 in gliomas are still unclear.Previous studies have shown that HOXC6 may regulate the Wnt signaling pathway,and the overactivation of the classic Wnt signaling pathway is closely related to the malignancy of gliomas.We know that Wnt inhibitor 1(WIF-1)is one of the Wnt antagonists.Whether HOXC6 affects the expression of Wnt signaling pathway antagonist WIF-1 to promote the occurrence and development of glioma specific molecular mechanisms remains to be further studied.We used TCGA and CGGA databases to determine the expression levels of HOXC6 and WIF-1 in various grades of gliomas and their relationship with the prognosis of gliomas.Real-time fluorescent PCR and Western blot were used to detect the expression of HOXC6 in various grades of glioma tissues and normal brain tissues.In order to explore the role of HOXC6 in glioma,we constructed a lentiviral vector that overexpressed HOXC6-sh RNA and transfected it in glioma U87 and U251 cell lines.Real-time fluorescent quantitative PCR and Western blot were used to detect the expression levels of HOXC6 and Wnt inhibitory factor-1(Wnt inhibitory factor-1,WIF-1)in glioma U87 cells after transfection of HOXC6-sh RNA.CCK-8 colony formation and Ed U analysis were used to detect the effects of HOXC6 on the proliferation of U87 and U251 cells,and flow cytometry was used to monitor the changes in cell cycle and apoptosis of U87 and U251 cell lines transfected with HOXC6-sh RNA.In vivo experiments were conducted to examine the carcinogenic effects of xenograft tumors in glioma tissues and the effect of HOXC6 on the prognostic value of nude mice.In this study,we found that HOXC6 is highly expressed in human glioma tissues,and the high expression of HOXC6 is related to the poor prognosis of GBM patients.We demonstrated that HOXC6 is highly expressed in human glioblastoma(GBM)tissues and three glioma cell lines.We also proved that by inhibiting cell cycle progression in G0/G1 phase and inducing apoptosis,HOXC6 knockdown significantly It inhibited the proliferation and colony forming ability of U87 and U251 cells.In addition,we learned from the analysis of experimental data that patients with gliomas with low WIF-1 expression have a better prognosis.Compared with the control group in in vitro experiments,WIF-1 was significantly higher at m RNA and protein levels after HOXC6-sh RNA transfection increase.These results are consistent with our predicted results.In addition,the xenotransplantation and immunohistochemistry results also show that when HOXC6 is inhibited,the growth of intracranial tumors and the expression of Ki-67 in nude mice are inhibited,while WIF-shows the opposite trend,WIF-1 The amount of expression is increased.The results of this study indicate that HOXC6 promotes the growth of glioma U87 and U251 cells by inhibiting the WIF-1/Wnt signaling pathway.HOXC6 may be a potential target for clinical treatment of glioma.