Preliminary Study On The Mechanism Of IFITM2 Regulating Invasion And Metastasis Of Colorectal Cancer

Background and ObjectiveColorectal cancer(CRC)is one of the most common causes of death of human malignancies in the world.According to statistics,more than 600,000 deaths are added each year[1],and more than 90%of patients with colorectal cancer die from cancer rectal cancer metastasis,so the prevention or effective intervention of colorectal cancer metastasis is considered a key issue in the treatment of colorectal cancer.Interferon-induced transmembrane protein 2(IFITM2)is also named 1-8D.The human IFITM2 gene is located on chromosome 11 and belongs to one of the interferon-induced transmembrane protein families.It is a type of cytokine.More and more studies have confirmed that IFITM can participate in the development of tumors by regulating cell proliferation,apoptosis and differentiation,and that IFITM family proteins are highly expressed in a variety of malignant tumors.In the early stage of the project,IFITM2 colorectal cancer-acting proteins were screened by analyzing the expression profile gene chip of transgenic mice’s colorectal cancer tissues.The research found that IFITM2 has a close relationship with colorectal cancer.Expression in cancer tissues and its mechanism in the development of colorectal cancer An in-depth understanding of the mechanism of the development of colorectal cancer will provide a theoretical basis for clinically developing effective treatments for colorectal cancer.Methods1.IFITM2 expression in colorectal cancerTCGA database was used to analyze the expression and significance of IFITM2 in colorectal cancer.Immunohistochemical staining was used to detect the expression of IFITM2 in colorectal cancer and paired normal intestinal mucosa tissue,and the relationship between IFITM2 and clinicopathological characteristics was analyzed.2.Construction of stable overexpression and interference with IFITM2 colorectal cancer cell lineThrough interference with SW480 and SW620 cell lines,real-time quantitative qPCR and Western blotting were used to screen for effective interference fragments,lentiviruses were used to construct stable interfering IFITM2 cell lines;and liposome transfection was used to construct overexpressing IFITM2 cell lines.3.The relationship between IFITM2 and epithelial-mesenchymal transition(EMT)in colorectal cancerThe effects of IFITM2 on EMT in colorectal cancer were verified by real-time quantitative qPCR and Western blotting to detect the expression of EMT markers in interference and overexpression IFITM2 cell lines.4.Preliminary exploration of the mechanism of IFITM2 and the development of colorectal cancerCo-localization of IFITM2 and MMP-9 was detected by immunohistochemical staining and immunofluorescence co-localization;real-time quantitative qPCR and Western blotting were used to verify the effects of interference and overexpression of IFITM2 on the downstream proteins MMP-9 and MMP-2 of the Wnt signaling pathway.Results1.IFITM2 is highly expressed in colorectal cancer tissues,and high expression of IFITM2 indicates a poor clinical prognosis.2.Interference and overexpression of IFITM2 colorectal cancer cell line was successfully constructed;real-time quantitative qPCR and Western blotting showed that after interfering with IFITM2 expression,EMT changes of colorectal cancer cells were suppressed,and overexpression of IFITM2 promoted EMT of colorectal cancer cells.3.Immunohistochemical staining and immunofluorescence co-localization showed the co-expression and co-localization of IFITM2 and MMP-9;real-time quantitative qPCR and Western blotting confirmed interference with IFITM2 expression,inhibiting MMP-9 and MMP-2 expression,and overexpression IFITM2 promotes the expression of MMP-9 and MMP-2.4.The abnormal expression of IFITM2 may affect the Wnt signaling pathway.The activation of Wnt pathway regulates the expression of MMP-9 and MMP-2 to affect the invasion and metastasis of colorectal cancer.Conclusions1.Immunohistochemical staining results and statistical analysis of data IFITM2 is highly expressed in colorectal cancer tissues.High expression of IFITM2 may promote colorectal cancer metastasis.2.Interfering with the expression of IFITM2,inhibiting EMT of colorectal cancer cells;overexpressing IFITM2,promoting EMT of colorectal cancer cells.3.Interfere with the expression of IFITM2 and inhibit the expression of MMP-9 and MMP-2;overexpress IFITM2 and promote the expression of MMP-9 and MMP-2.4.IFITM2 activates Wnt signaling pathway by regulating β-catenin,thereby regulating the expression of MMP-9 and MMP-2 to affect the invasion and metastasis of colorectal cancer.