Transcription Factor Gli1 Promotes Colorectal Cancer Cell Proliferation Through Activating FoxM1

Background: Colorectal cancer(CRC)in both developed and developing countries is a highly fatal cancer.The incidence rate of colorectal cancer in China also increased year by year in China.Current treatment are surgery oncolorectal resection,supplemented by other treatments such as interventional therapy,chemotherapy,radiotherapy and molecular targeted therapy.Looking for a specific target molecule is the direction of scientific research.Found biological molecules associated with colorectal cancer are many,but research on the pathogenesis is still no systematic conclusion.To further clarify the mechanism of development and progression of colorectal cancer,we need to identify a specific target molecule.Hedgehog signaling pathway involved in the regulation of cell,embryonic development,and the stability of the internal environment.Hedgehog pathway abnormal activation can lead to cancer,including colorectal cancer.Gli1 as end-effector of the Hedgehog pathway,into nuclear activates a series of downstream target genes,studies have reported than Gli1 promote the development and progression of colorectal cancer.FoxM1 affects mitosis and cell cyc le factors,and regulates the transition of G1-S and G2-M.FoxM1 overexpression is considered to be an important symbol of many malignant tumors.The interaction between the Hedgehog pathway and FoxM1 plays a crucial role in finding a related target molecule involved in the development,diagnosis and treatment of colorectal cancer.Objectives:1.Research the role of FoxM1 on the proliferation of colon cancer cells.2.Analyze the molecular mechanism of regulation of Gli1 on FoxM1.3.Clarify Gli1 promote C RC cells proliferation through activating FoxM1.Methods:1.FoxM1 expression in cancer tissues and normal tissues of colorectal cancer tissues were performed by immunohistochemistry(IHC)and Western Blot(WB).2.The influence of FoxM1 on colorectal cancer cells was processed by Brdu and clone formation experiments.3.The interaction between FoxM1 and Gli1 was analyzed by ChIP and Dual-luciferase experiments.4.Cell cycle analysis verify the regulation of Gli1-FoxM1 axis in CRC cells.Results:1.FoxM1 highly expressed in colon cancer tissues compared with the adjacent normal tissues.2.Overexpression of FoxM1 can promote the proliferation of colon cancer cells,and interfere FoxM1 can inhibit colon cancer cell proliferation.3.Gli1 through bind to the promoter region of FoxM1 to activate FoxM1.4.The regulation of Gli1 on CRC cells proliferation and the cell cycle G1,G2 phase can be blocked by FoxM1 inhibitor,indicated that FoxM1 mediated the regulation of Gli1 on colorectal cancer cell proliferation.Conclusion: Gli1 by directly binding to the promoter region of FoxM1 regulates its transcription,forming hedgehog-Gli1-FoxM1 signal axis promotes cell proliferation in colorectal.FoxM1 as Gli1 direct target,can be taken as new clinical colorectal cancer treatment target.