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Cell Cycle Progression in STHdh(Q111)/Hdh(Q111) Cells, a Cell Model for Huntington's Disease Mediated by microRNA-19a, microRNA-146a and microRNA-432.\nSeveral indirect evidences are available to indicate that abnormalities in cell cycle may contribute to pathogenesis of Huntington's disease (HD). Here, we show that the cell cycle progression in STsdh(Q111)/Hdh(Q111)cells, a cell model of HD, is delayed in S and G2-M phases compared to control STHdhQ7/HdhQ7cells. Expression of 17 genes, like PCNA and CHEK1, was increased in STHdh(Q111)/Hdh(Q111)cells. Increased expressions of PCNA, CHEK1 and CCNA2, and an enhanced phosphorylation of Rb1 were observed in primary cortical neurons expressing mutant N-terminal huntingtin (HTT), R6/2 mice and STHdh(Q111)/Hdh(Q111) cells. This increase in the expressions of PCNA, CHEK1 and CCNA2 was found to be the result of decreased expressions of miR-432, miR-146a, and (miR-19a and miR-146a), respectively. Enhanced apoptosis was observed at late S phase and G2-M phase in STHdh(Q111)/Hdh(Q111)cells. Exogenous expressions of these miRNAs in STHdh(Q111)/Hdh(Q111) cells rescued the abnormalities in cell cycle and apoptosis. We also observed that inhibitors of cell cycle could decrease cell death in a cell model of HD. Based on these results obtained in cell and animal model of HD, we propose that inhibition of cell cycle either by miRNA expressions or by using inhibitors could be a potential approach for the treatment of HD."}

{"project":"UseCases_ArguminSci_Discourse","denotations":[{"id":"T1","span":{"begin":0,"end":158},"obj":"DRI_Background"},{"id":"T2","span":{"begin":159,"end":305},"obj":"DRI_Challenge"},{"id":"T3","span":{"begin":306,"end":474},"obj":"DRI_Outcome"},{"id":"T4","span":{"begin":475,"end":564},"obj":"DRI_Background"},{"id":"T5","span":{"begin":565,"end":783},"obj":"DRI_Background"},{"id":"T6","span":{"begin":784,"end":957},"obj":"DRI_Outcome"},{"id":"T7","span":{"begin":958,"end":1051},"obj":"DRI_Background"},{"id":"T8","span":{"begin":1052,"end":1175},"obj":"DRI_Approach"},{"id":"T9","span":{"begin":1176,"end":1271},"obj":"DRI_Outcome"},{"id":"T10","span":{"begin":1272,"end":1482},"obj":"DRI_Approach"}],"text":"Delayed Cell Cycle Progression in STHdh(Q111)/Hdh(Q111) Cells, a Cell Model for Huntington's Disease Mediated by microRNA-19a, microRNA-146a and microRNA-432.\nSeveral indirect evidences are available to indicate that abnormalities in cell cycle may contribute to pathogenesis of Huntington's disease (HD). Here, we show that the cell cycle progression in STsdh(Q111)/Hdh(Q111)cells, a cell model of HD, is delayed in S and G2-M phases compared to control STHdhQ7/HdhQ7cells. Expression of 17 genes, like PCNA and CHEK1, was increased in STHdh(Q111)/Hdh(Q111)cells. Increased expressions of PCNA, CHEK1 and CCNA2, and an enhanced phosphorylation of Rb1 were observed in primary cortical neurons expressing mutant N-terminal huntingtin (HTT), R6/2 mice and STHdh(Q111)/Hdh(Q111) cells. This increase in the expressions of PCNA, CHEK1 and CCNA2 was found to be the result of decreased expressions of miR-432, miR-146a, and (miR-19a and miR-146a), respectively. Enhanced apoptosis was observed at late S phase and G2-M phase in STHdh(Q111)/Hdh(Q111)cells. Exogenous expressions of these miRNAs in STHdh(Q111)/Hdh(Q111) cells rescued the abnormalities in cell cycle and apoptosis. We also observed that inhibitors of cell cycle could decrease cell death in a cell model of HD. Based on these results obtained in cell and animal model of HD, we propose that inhibition of cell cycle either by miRNA expressions or by using inhibitors could be a potential approach for the treatment of HD."}