Although the role of copper (Cu) in promoting KRas- or BRaf-mutation driven cancers via activating MEK1/2 kinases is known, the mechanism by which the copper transporter SLC31A1 (CTR1) is upregulated in pancreatic can...Although the role of copper (Cu) in promoting KRas- or BRaf-mutation driven cancers via activating MEK1/2 kinases is known, the mechanism by which the copper transporter SLC31A1 (CTR1) is upregulated in pancreatic cancer (PDAC, KRas mutation) is not defined. In this study, we provide evidence that MEK signal maintains a high level of SLC31A1 through silencing the expression of miR-124-3P (miR-124) via a novel MEK-DNMT1-miR-124 feedback loop in PDAC cells. Further, we reveal that miR-124 directly targets suppression of SLC31A1, and miR-124 introduction together with tetrathiomolybdate (TM) treatment hampered pancreatic cancer growth in vitro and in vivo. Our results demonstrate that a SLC31A1-MEK-DNMT1-miR-124 feedback loop is an important pathway to maintain copper absorption and promote pancreatic cancer progression, and we hope to provide a Cu-chelation as an adjuvant treatment strategy, to block the progression in Kras mutant PDAC patients.展开更多
Dear Editor,In most flowering plants, the stigma of the flower represents the barrier that prevents any unrelated or incompatible （genetically similar） pollen from germination and fertilizing the ovule, leading to e...Dear Editor,In most flowering plants, the stigma of the flower represents the barrier that prevents any unrelated or incompatible （genetically similar） pollen from germination and fertilizing the ovule, leading to either defective or genetically unfavorable embryos. In Brassicaceae, self-incompatibility （SI） is a genetic mechanism in the stigmas that can discern compatible versus incompatible mate （pollen）, in turn, rejecting self or incompatible pollen, while allowing non-self or compatible pollen to develop successfully to fertilize the ovules. Thus, stigmas have evolved complex mechanisms and specialized proteins to reject incompatible mates and to recognize and accept compatible pollen （Doucet et al., 2016）. The fact that SI has been shown to exclusively operate in the stigmas temporally before and during anthesis （Kandasamy et al., 1993） indicates that multiple metabolic pathways essential for pollination exist in these stigmatic papillary cells.展开更多
基金supported by The National Natural Science Foundation of China(No.32072801)Fundamental Research Funds for the Central Universities of China(No.2572020DY12).
文摘Although the role of copper (Cu) in promoting KRas- or BRaf-mutation driven cancers via activating MEK1/2 kinases is known, the mechanism by which the copper transporter SLC31A1 (CTR1) is upregulated in pancreatic cancer (PDAC, KRas mutation) is not defined. In this study, we provide evidence that MEK signal maintains a high level of SLC31A1 through silencing the expression of miR-124-3P (miR-124) via a novel MEK-DNMT1-miR-124 feedback loop in PDAC cells. Further, we reveal that miR-124 directly targets suppression of SLC31A1, and miR-124 introduction together with tetrathiomolybdate (TM) treatment hampered pancreatic cancer growth in vitro and in vivo. Our results demonstrate that a SLC31A1-MEK-DNMT1-miR-124 feedback loop is an important pathway to maintain copper absorption and promote pancreatic cancer progression, and we hope to provide a Cu-chelation as an adjuvant treatment strategy, to block the progression in Kras mutant PDAC patients.
文摘Dear Editor,In most flowering plants, the stigma of the flower represents the barrier that prevents any unrelated or incompatible （genetically similar） pollen from germination and fertilizing the ovule, leading to either defective or genetically unfavorable embryos. In Brassicaceae, self-incompatibility （SI） is a genetic mechanism in the stigmas that can discern compatible versus incompatible mate （pollen）, in turn, rejecting self or incompatible pollen, while allowing non-self or compatible pollen to develop successfully to fertilize the ovules. Thus, stigmas have evolved complex mechanisms and specialized proteins to reject incompatible mates and to recognize and accept compatible pollen （Doucet et al., 2016）. The fact that SI has been shown to exclusively operate in the stigmas temporally before and during anthesis （Kandasamy et al., 1993） indicates that multiple metabolic pathways essential for pollination exist in these stigmatic papillary cells.
