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
Objective： To study apoptotic effects of synthetic retinoic acid 6-[3-（1-adamantyl）-4-hydroxyphenyl]-2-naphthalene carboxylic acid（AHPN） on human skin malignant melanoma A375 cells in comparison with the natural ...Objective： To study apoptotic effects of synthetic retinoic acid 6-[3-（1-adamantyl）-4-hydroxyphenyl]-2-naphthalene carboxylic acid（AHPN） on human skin malignant melanoma A375 cells in comparison with the natural ligand all-trans-retinoic acid（ATRA） in vitro and the mechanisms related to the actions of AHPN. Methods：MTT assay was used to determine the anti-proliferative effects of AHPN and ATRA on A375 cells. Flow cytometry was performed to investigate the influence of AHPN and ATRA on cell cycle and cell apoptosis. In addition, transfection and luciferase activity assays were employed to explore the mechanisms of how AHPN executes its proapoptotic function. Results：Firstly, AHPN promoted apoptosis and GI arrest in A375 cells compared with ATRA. Secondly, the activity of NF-K B in A375 cells treated with AHPN increased 2-3 times compared with solvent DMSO treatment. Conclusion：AHPN, in comparison with ATRA, is a more effective alternative for therapy of malignant melanoma. The potentially proapoptotic function of AHPN requires activation of NF-K B.展开更多
Tumor suppressor ARF can induce cell cycle arrest or apoptosis by activating p53. In order to explore the molecular mechanism of the induction of apoptosis by p14ARF, a human melanoma cell model overexpressing p14ARF ...Tumor suppressor ARF can induce cell cycle arrest or apoptosis by activating p53. In order to explore the molecular mechanism of the induction of apoptosis by p14ARF, a human melanoma cell model overexpressing p14ARF was constructed. Present study indicated that in the cells overex-pressing p14ARF, p53 was accumulated in nucleus while it dispersed in cytosol in the control cells. Irradiated with g-ray, overexpressing p14ARF promoted the apoptosis of A375 cells, triggered Smac release from mitochondria to cytosol, and increased the expression of p53, Bax, Caspase-3, Caspase-9, p21cip1 and p27kip1. However, the protein level of Bcl-2 and phospho-ERK was down-regulated. These results suggested a possible mechanism of p14ARF in promotion of apoptosis.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.
文摘Objective： To study apoptotic effects of synthetic retinoic acid 6-[3-（1-adamantyl）-4-hydroxyphenyl]-2-naphthalene carboxylic acid（AHPN） on human skin malignant melanoma A375 cells in comparison with the natural ligand all-trans-retinoic acid（ATRA） in vitro and the mechanisms related to the actions of AHPN. Methods：MTT assay was used to determine the anti-proliferative effects of AHPN and ATRA on A375 cells. Flow cytometry was performed to investigate the influence of AHPN and ATRA on cell cycle and cell apoptosis. In addition, transfection and luciferase activity assays were employed to explore the mechanisms of how AHPN executes its proapoptotic function. Results：Firstly, AHPN promoted apoptosis and GI arrest in A375 cells compared with ATRA. Secondly, the activity of NF-K B in A375 cells treated with AHPN increased 2-3 times compared with solvent DMSO treatment. Conclusion：AHPN, in comparison with ATRA, is a more effective alternative for therapy of malignant melanoma. The potentially proapoptotic function of AHPN requires activation of NF-K B.
文摘Tumor suppressor ARF can induce cell cycle arrest or apoptosis by activating p53. In order to explore the molecular mechanism of the induction of apoptosis by p14ARF, a human melanoma cell model overexpressing p14ARF was constructed. Present study indicated that in the cells overex-pressing p14ARF, p53 was accumulated in nucleus while it dispersed in cytosol in the control cells. Irradiated with g-ray, overexpressing p14ARF promoted the apoptosis of A375 cells, triggered Smac release from mitochondria to cytosol, and increased the expression of p53, Bax, Caspase-3, Caspase-9, p21cip1 and p27kip1. However, the protein level of Bcl-2 and phospho-ERK was down-regulated. These results suggested a possible mechanism of p14ARF in promotion of apoptosis.
