BACKGROUND The human microRNA 375(MIR375)is significantly downregulated in human colorectal cancer(CRC)and we have previously shown that MIR375 is a CRCassociated miRNA.The metadherin(MTDH)is a candidate target gene o...BACKGROUND The human microRNA 375(MIR375)is significantly downregulated in human colorectal cancer(CRC)and we have previously shown that MIR375 is a CRCassociated miRNA.The metadherin(MTDH)is a candidate target gene of MIR375.AIM To investigate the interaction and function between MIR375 and MTDH in human CRC.METHODS A luciferase reporter system was used to confirm the effect of MIR375 on MTDH expression.The expression levels of MIR375 and the target genes were evaluated by quantitative RT-PCR(qRT-PCR),western blotting,or immunohistochemistry.RESULTS MTDH expression was found to be upregulated in human CRC tissues compared to that in healthy controls.We show that MIR375 regulates the expression of many genes involved in the MTDH-mediated signal transduction pathways[BRAF-MAPK and phosphatidylinositol-4,5-biphosphate-3-kinase catalytic subunit alpha(PIK3CA)-AKT]in CRC cells.Upregulated MTDH expression levels were found to inhibit NF-κB inhibitor alpha,which further upregulated NFKB1 and RELA expression in CRC cells.CONCLUSION Our findings suggest that suppressing MIR375 expression in CRC regulates cell proliferation and angiogenesis by increasing MTDH expression.Thus,MIR375 may be of therapeutic value in treating human CRC.展开更多
基金Supported by a grant from the National Research Foundation of Korea,No.2017R1A2B4004801
文摘BACKGROUND The human microRNA 375(MIR375)is significantly downregulated in human colorectal cancer(CRC)and we have previously shown that MIR375 is a CRCassociated miRNA.The metadherin(MTDH)is a candidate target gene of MIR375.AIM To investigate the interaction and function between MIR375 and MTDH in human CRC.METHODS A luciferase reporter system was used to confirm the effect of MIR375 on MTDH expression.The expression levels of MIR375 and the target genes were evaluated by quantitative RT-PCR(qRT-PCR),western blotting,or immunohistochemistry.RESULTS MTDH expression was found to be upregulated in human CRC tissues compared to that in healthy controls.We show that MIR375 regulates the expression of many genes involved in the MTDH-mediated signal transduction pathways[BRAF-MAPK and phosphatidylinositol-4,5-biphosphate-3-kinase catalytic subunit alpha(PIK3CA)-AKT]in CRC cells.Upregulated MTDH expression levels were found to inhibit NF-κB inhibitor alpha,which further upregulated NFKB1 and RELA expression in CRC cells.CONCLUSION Our findings suggest that suppressing MIR375 expression in CRC regulates cell proliferation and angiogenesis by increasing MTDH expression.Thus,MIR375 may be of therapeutic value in treating human CRC.
