The Study On The Expression Of FOXM1 In Colorectal Cancer And The Role Of FOXM1 To Colon Cancer Cells Proliferation And Metastasis

[Objectives]To investigate the expression of FOXM1 in colorectal cancer(CRC) and the relevance of FOXM1 overexpression in CRC patients. Using small interfering RNA technology targeting knockdown the expression of FOXM1 in colon cancer cells, to evaluate the roles of the expression of FOXM1 in colon cancer cells proliferation and metastasis, furtherly to provide a theoretical basis for molecular target for colon cancer treatment. [Methods]In our study, we investigated FOXM1 protein expression in 87 CRC tissue specimens and adjacent paired normal colorectal cancer tissues by immunohistochemical analysis. Then we collected the information of CRC patients and analyzed the relationship between FOXM1 expression levers and clinicopathologic parameters. We selected the highest expression of FOXM1 in several colon cancer cells through real-time PCR and western blot. Then we transfected FOXM1 specific shRNA into colon cancer cells to examine effect of FOXM1 on proliferation, colony formation, migration and invasion in vitro. Western blotting and real-time PCR were used to detect the protein and mRNA expression of FOXM1 and EMT-related markers. [Results]1.The FOXM1 immunohistochemical staining results showed that in 87 CRC tissues, 52 showed strong staining and 35 showed negative or weak staining, the moderate and strong positive rate was 59.8%, while in adjacent paired normal colorectal cancer tissues, 23 showed moderate and strong staining, 64 were negative or weak, the positive rate was 26.4%, the difference was significant(P<0.01), which suggested that FOXM1 was overexpressed in CRC tissues than normal colorectal tissues. FoxM1 overexpression was significantly associated with lymph node metastasis(P< 0.001), and tumor recurrence(P< 0.001), however, FoxM1 expression level was not associated with other clinicopathologic features, such as age, gender, tumor size, tumor location, TNM stages and histological differentiation(all p>0.05).2.Real-time PCR and Western blotting results showed that FOXM1 was over-expressed in SW620 cells, and downregulation of FOXM1 in SW620 cells by shRNA approach inhibited cell growth, clonogenicity, migration and invasion in vitro. In addition, decreased FOXM1 expression in SW620 cells reversed the acquisition of EMT phenotype by up-regulating E-cadherin, as well as reduction Vimentin and Snail expressions at protein and mRNA levels. [Conclusions]The expression of FOXM1 in CRC tissues was significantly elevated compared with the adjacent paired normal colorectal cancer tissues, which suggested that FOXM1 might play a role in the tumorigenesis and progression of colorectal cancer cells; the downexpression of FOXM1 inhibited colon cancer cell proliferation, meanwhile, FOXM1 may regulate CRC cells metastasis through EMT program and FOXM1 may be a potential target for treatment of CRC.