MicroRNAs are small endogenously expressed RNA molecules which are involved in the process of silencing gene expression through translational regulation.The polycistronic miR-17-92 cluster is the first microRNA cluste...MicroRNAs are small endogenously expressed RNA molecules which are involved in the process of silencing gene expression through translational regulation.The polycistronic miR-17-92 cluster is the first microRNA cluster shown to play a role in tumorigenesis.It has two other paralogs in the human genome,the miR-106b-25 cluster and the miR-106a-363 cluster.Collectively,the microRNAs encoded by these clusters can be further grouped based on the seed sequences into four families,namely the miR-17,the miR-92,the miR-18and the miR-19 families.Over-expression of the miR-106b-25 and miR-17-92 clusters has been reported not only during the development of cirrhosis but also subsequently during the development of hepatocellular carcinoma.Members of these clusters have also been shown to affect the replication of hepatitis B and hepatitis C viruses.Various targets of these microRNAs have been identified,and these targets are involved in tumor growth,cell survival and metastasis.In this review,we first describe the regulation of these clusters by c-Myc and E2F1,and how the members of these clusters inturn regulate E2F1 expression forming an auto-regulatory loop.In addition,the roles of the various members of the clusters in affecting relevant target gene expression in the pathogenesis of hepatocellular carcinoma will also be discussed.展开更多
目的:血管生成是肿瘤生长和转移的关键介质,CDC25B在包括三阴性乳腺癌(Triple-Negative Breast Cancer,TNBC)等恶性肿瘤作为肿瘤癌基因,但其对血管生成的生物学作用知之甚少,本研究旨在探讨CDC25B在TNBC血管生成中的确切功能和作用机制...目的:血管生成是肿瘤生长和转移的关键介质,CDC25B在包括三阴性乳腺癌(Triple-Negative Breast Cancer,TNBC)等恶性肿瘤作为肿瘤癌基因,但其对血管生成的生物学作用知之甚少,本研究旨在探讨CDC25B在TNBC血管生成中的确切功能和作用机制。方法:生信数据库分析CDC25B及其上游调控分子miR-141-3p在TNBC肿瘤组织中的表达,采用qRT-PCR分析CDC25B和miR-141-3p在TNBC细胞系中的表达。利用CCK-8和血管形成实验分析HUVEC细胞的增殖和血管形成能力,并通过Western blot检测VEGFA、VEGFR-2和VEGFR-3蛋白的表达。双荧光素酶报告实验被用于探索CDC25B和miR-141-3p之间的特异性相互作用。结果:本研究发现CDC25B在TNBC中表达上调,其高表达可以激活VEGF信号通路,沉默CDC25B后显著抑制了HUVEC细胞的增殖和血管生成,并降低了VEGFA、VEGFR-2和VEGFR-3蛋白的表达。此外,miR-141-3p在TNBC中表达下调,可以靶向抑制CDC25B的表达。过表达CDC25B可以逆转miR-141-3p过表达对HUVEC细胞增殖和血管生成的抑制作用。结论:miR-141-3p靶向CDC25B抑制VEGF通路抑制TNBC血管生成,为miR-141-3p/CDC25B/VEGF通路可能作为TNBC抗血管生成治疗的新选择提供理论依据。展开更多
文摘MicroRNAs are small endogenously expressed RNA molecules which are involved in the process of silencing gene expression through translational regulation.The polycistronic miR-17-92 cluster is the first microRNA cluster shown to play a role in tumorigenesis.It has two other paralogs in the human genome,the miR-106b-25 cluster and the miR-106a-363 cluster.Collectively,the microRNAs encoded by these clusters can be further grouped based on the seed sequences into four families,namely the miR-17,the miR-92,the miR-18and the miR-19 families.Over-expression of the miR-106b-25 and miR-17-92 clusters has been reported not only during the development of cirrhosis but also subsequently during the development of hepatocellular carcinoma.Members of these clusters have also been shown to affect the replication of hepatitis B and hepatitis C viruses.Various targets of these microRNAs have been identified,and these targets are involved in tumor growth,cell survival and metastasis.In this review,we first describe the regulation of these clusters by c-Myc and E2F1,and how the members of these clusters inturn regulate E2F1 expression forming an auto-regulatory loop.In addition,the roles of the various members of the clusters in affecting relevant target gene expression in the pathogenesis of hepatocellular carcinoma will also be discussed.
文摘目的:血管生成是肿瘤生长和转移的关键介质,CDC25B在包括三阴性乳腺癌(Triple-Negative Breast Cancer,TNBC)等恶性肿瘤作为肿瘤癌基因,但其对血管生成的生物学作用知之甚少,本研究旨在探讨CDC25B在TNBC血管生成中的确切功能和作用机制。方法:生信数据库分析CDC25B及其上游调控分子miR-141-3p在TNBC肿瘤组织中的表达,采用qRT-PCR分析CDC25B和miR-141-3p在TNBC细胞系中的表达。利用CCK-8和血管形成实验分析HUVEC细胞的增殖和血管形成能力,并通过Western blot检测VEGFA、VEGFR-2和VEGFR-3蛋白的表达。双荧光素酶报告实验被用于探索CDC25B和miR-141-3p之间的特异性相互作用。结果:本研究发现CDC25B在TNBC中表达上调,其高表达可以激活VEGF信号通路,沉默CDC25B后显著抑制了HUVEC细胞的增殖和血管生成,并降低了VEGFA、VEGFR-2和VEGFR-3蛋白的表达。此外,miR-141-3p在TNBC中表达下调,可以靶向抑制CDC25B的表达。过表达CDC25B可以逆转miR-141-3p过表达对HUVEC细胞增殖和血管生成的抑制作用。结论:miR-141-3p靶向CDC25B抑制VEGF通路抑制TNBC血管生成,为miR-141-3p/CDC25B/VEGF通路可能作为TNBC抗血管生成治疗的新选择提供理论依据。
