目的总结microRNA-200(miR-200)家族在三阴性乳腺癌(triple-negative breast cancer,TNBC)中的研究进展。方法系统检索并阅读国内外的相关文献,对近年来miR-200家族在TNBC中的研究进展进行综述。结果miR-200家族在TNBC的增殖、侵袭转移...目的总结microRNA-200(miR-200)家族在三阴性乳腺癌(triple-negative breast cancer,TNBC)中的研究进展。方法系统检索并阅读国内外的相关文献,对近年来miR-200家族在TNBC中的研究进展进行综述。结果miR-200家族在TNBC的增殖、侵袭转移及治疗抵抗性中发挥重要作用,并可作为潜在的治疗靶点和生物预测因子。不同的miR-200家族成员及其差异表达介导不同的靶向作用,这可能与信号通路及细胞环境差异有关。结论miR-200家族在TNBC的发生和发展过程中具有关键性的调控作用,这有望为TNBC的治疗及预后评估提供新思路,但其作用机制仍待进一步的深入研究。展开更多
MicroRNAs(miRNAs)have been widely implicated in immune regulation,but evidence for the coordinated function of paralogous miRNA clusters remains scarce.Here,by using genetically modified mice with individual or combin...MicroRNAs(miRNAs)have been widely implicated in immune regulation,but evidence for the coordinated function of paralogous miRNA clusters remains scarce.Here,by using genetically modified mice with individual or combined cluster deficiencies,we found that three paralogous clusters of the miR-17-92 family of miRNAs collectively suppressed IL-12 production in macrophages.Accordingly,miR-17-92 family miRNAs deficiencies resulted in heightened production of IL-12 and thus enhanced the host defense against intracellular pathogen Listeria monocytogenes in vivo.Mechanistically,different members of the miR-17-92 family of miRNAs acted on a common target,PTEN,to inhibit IL-12 expression by modulating the PI3K-Akt-GSK3 pathway.In addition,the expression of miR-17-92 family miRNAs was collectively inhibited by the transcription factor RBP-J,and RBP-J-associated macrophage functional defects were genetically rescued by deleting three clusters of miR-17-92 family miRNAs on a RBP-J null background.Thus,our results illustrated key roles of three clusters of miR-17-92 family miRNAs in cooperatively controlling IL-12-mediated immune responses and identified miR-17-92 family miRNAs as functional targets of RBP-J in macrophages.展开更多
文摘目的总结microRNA-200(miR-200)家族在三阴性乳腺癌(triple-negative breast cancer,TNBC)中的研究进展。方法系统检索并阅读国内外的相关文献,对近年来miR-200家族在TNBC中的研究进展进行综述。结果miR-200家族在TNBC的增殖、侵袭转移及治疗抵抗性中发挥重要作用,并可作为潜在的治疗靶点和生物预测因子。不同的miR-200家族成员及其差异表达介导不同的靶向作用,这可能与信号通路及细胞环境差异有关。结论miR-200家族在TNBC的发生和发展过程中具有关键性的调控作用,这有望为TNBC的治疗及预后评估提供新思路,但其作用机制仍待进一步的深入研究。
基金supported by the Ministry of Science and Technology of China National Key Research Projects(2015CB943201 to X.H.and 2015CB943200 to L.W.)National Natural Science Foundation of China grants(31821003,31725010,81571580,91642115,and 81661130161 to X.H.and 31330027 to LW.)+2 种基金funds from Tsinghua-Peking Center for Life Sciences(X.H.,L.W.,and XZ)funds from the Institute for Immunology at Tsinghua University(X.H.and L.W.)funds from the National Institutes of Health(BZ).
文摘MicroRNAs(miRNAs)have been widely implicated in immune regulation,but evidence for the coordinated function of paralogous miRNA clusters remains scarce.Here,by using genetically modified mice with individual or combined cluster deficiencies,we found that three paralogous clusters of the miR-17-92 family of miRNAs collectively suppressed IL-12 production in macrophages.Accordingly,miR-17-92 family miRNAs deficiencies resulted in heightened production of IL-12 and thus enhanced the host defense against intracellular pathogen Listeria monocytogenes in vivo.Mechanistically,different members of the miR-17-92 family of miRNAs acted on a common target,PTEN,to inhibit IL-12 expression by modulating the PI3K-Akt-GSK3 pathway.In addition,the expression of miR-17-92 family miRNAs was collectively inhibited by the transcription factor RBP-J,and RBP-J-associated macrophage functional defects were genetically rescued by deleting three clusters of miR-17-92 family miRNAs on a RBP-J null background.Thus,our results illustrated key roles of three clusters of miR-17-92 family miRNAs in cooperatively controlling IL-12-mediated immune responses and identified miR-17-92 family miRNAs as functional targets of RBP-J in macrophages.