Microvesicles (MVs) or shedding membrane vesicles have recently been described as a novel model of intercellular communication. Previously, MVs were considered as unnecessary or secreted cellular debris, but MVs have ...Microvesicles (MVs) or shedding membrane vesicles have recently been described as a novel model of intercellular communication. Previously, MVs were considered as unnecessary or secreted cellular debris, but MVs have lately been described as having roles in a variety of biological functions, such as cell homeostasis and the cellular processes involved in the oncogenesis of many types of tumors. Carrying several key molecules that contribute to tumor development and progression, similar to mRNAs, microRNAs and other non-coding RNAs, DNA and even small proteins, MVs can be considered as a ubiquitous form of novel cell communication that is present in most somatic cells. Although tumor-derived MVs have been demonstrated in different types of cancers, the literature data on MVs in primary central nervous system (CNS) tumors are relatively scarce. In this review, we address the involvement of MVs in diffuse astrocytomas, particularly glioblastomas, as well as oligodendrogliomas and medulloblastomas. We placed particular focus on the cellular crosstalk between tumor and “normal” cells, the putative mechanisms how the tumor microenvironment is modulated and the spread of aggressive phenotypes. Additionally, a better understanding of the participation of tumor-derived MVs in the regulation of key cancer pathways will offer new insights into tumor pathogenesis and the mechanisms of multidrug resistance, and may help to develop new strategies for novel therapies against these infiltrative CNS tumors.展开更多
Constitutive hedgehog （Hh） signaling is associated with the genesis of medulloblastomas （MB）. The objective of this study is to identify special microRNAs （miRNAs） regulated by the Hh pathway, and to clarify the...Constitutive hedgehog （Hh） signaling is associated with the genesis of medulloblastomas （MB）. The objective of this study is to identify special microRNAs （miRNAs） regulated by the Hh pathway, and to clarify the role of miRNAs during the genesis of MB induced by sustained Hh activation. In the primary screening, we used stemloop RT-PCR to test the expression of 90 different miRNAs in the wildtype （WT） and Ptc-/- MEF cell lines. In the secondary screening, the miRNAs screened from the first screening were validated in the Sufu-/- MEF cell lines. We then verified the expression of miRNAs both in the normal cerebellar tissues and the MB induced by activated Hh pathway, and examined the expression of the other 21 miRNA members of the miR-154 cluster in the MB and normal cerebellum. In the first screening, 13 miRNAs showed significant differential expression in WT and Ptc-/- MEF cell lines, while 10 of them had significant difference in the Sufu-/- MEF cell line. Compared to the normal mouse cerebellum, only 2 miRNAs in 15 miRNAs were differentially expressed between the MB and normal cerebellar tissues. Among 21 members of the miR-154 cluster, 6 miRNAs were downregulated in the MB. Our study demonstrated that miR-154 may be regulated by the Hh pathway, and the activation of the Hh pathway led to the downregulation of the miR-154 cluster, resulting in the genesis of MB.展开更多
Background MicroRNAs （miRNAs） are small noncoding regulatory RNAs whose aberrant expression may be observed in many malignancies. However, few data are yet available on human primary medulloblastomas. This work aime...Background MicroRNAs （miRNAs） are small noncoding regulatory RNAs whose aberrant expression may be observed in many malignancies. However, few data are yet available on human primary medulloblastomas. This work aimed to identify that whether miRNAs would be aberrantly expressed in tumor tissues compared with non-tumorous cerebellum tissues from same patients, and to explore a possible role during carcinogenesis. Methods A high throughput microRNA microarray was performed in human primary medulloblastoma specimens to investigate differentially expressed miRNAs, and some miRNAs were validated using real-time quantitative RT-PCR method. In addition, the predicted target genes for the most significantly downor up-regulated miRNAs were analyzed by using a newly modified ensemble algorithm. Results Nine miRNA species were differentially expressed in medulloblastoma specimens versus normal non-tumorous cerebellum tissues. Of these, 4 were over expressed and 5 were under expressed. The changes ranged from 0.02-fold to 6.61-fold. These findings were confirmed using real-time quantitative RT-PCR for most significant deregulated miRNAs （miR-17, miR-100, miR-106b, and miR-218） which are novel and have not been previously published. Interestingly, most of the predicted target genes for these miRNAs were involved in medulloblastoma carcinogenesis. Conclusions MJRNAs are differentially expressed between human medulloblastoma and non-tumorous cerebellum tissue. MiRNAs may play a role in the tumorigenesis of medulloblastoma and maybe serve as potential targets for novel therapeutic strategies in future.展开更多
文摘Microvesicles (MVs) or shedding membrane vesicles have recently been described as a novel model of intercellular communication. Previously, MVs were considered as unnecessary or secreted cellular debris, but MVs have lately been described as having roles in a variety of biological functions, such as cell homeostasis and the cellular processes involved in the oncogenesis of many types of tumors. Carrying several key molecules that contribute to tumor development and progression, similar to mRNAs, microRNAs and other non-coding RNAs, DNA and even small proteins, MVs can be considered as a ubiquitous form of novel cell communication that is present in most somatic cells. Although tumor-derived MVs have been demonstrated in different types of cancers, the literature data on MVs in primary central nervous system (CNS) tumors are relatively scarce. In this review, we address the involvement of MVs in diffuse astrocytomas, particularly glioblastomas, as well as oligodendrogliomas and medulloblastomas. We placed particular focus on the cellular crosstalk between tumor and “normal” cells, the putative mechanisms how the tumor microenvironment is modulated and the spread of aggressive phenotypes. Additionally, a better understanding of the participation of tumor-derived MVs in the regulation of key cancer pathways will offer new insights into tumor pathogenesis and the mechanisms of multidrug resistance, and may help to develop new strategies for novel therapies against these infiltrative CNS tumors.
文摘Constitutive hedgehog （Hh） signaling is associated with the genesis of medulloblastomas （MB）. The objective of this study is to identify special microRNAs （miRNAs） regulated by the Hh pathway, and to clarify the role of miRNAs during the genesis of MB induced by sustained Hh activation. In the primary screening, we used stemloop RT-PCR to test the expression of 90 different miRNAs in the wildtype （WT） and Ptc-/- MEF cell lines. In the secondary screening, the miRNAs screened from the first screening were validated in the Sufu-/- MEF cell lines. We then verified the expression of miRNAs both in the normal cerebellar tissues and the MB induced by activated Hh pathway, and examined the expression of the other 21 miRNA members of the miR-154 cluster in the MB and normal cerebellum. In the first screening, 13 miRNAs showed significant differential expression in WT and Ptc-/- MEF cell lines, while 10 of them had significant difference in the Sufu-/- MEF cell line. Compared to the normal mouse cerebellum, only 2 miRNAs in 15 miRNAs were differentially expressed between the MB and normal cerebellar tissues. Among 21 members of the miR-154 cluster, 6 miRNAs were downregulated in the MB. Our study demonstrated that miR-154 may be regulated by the Hh pathway, and the activation of the Hh pathway led to the downregulation of the miR-154 cluster, resulting in the genesis of MB.
文摘Background MicroRNAs （miRNAs） are small noncoding regulatory RNAs whose aberrant expression may be observed in many malignancies. However, few data are yet available on human primary medulloblastomas. This work aimed to identify that whether miRNAs would be aberrantly expressed in tumor tissues compared with non-tumorous cerebellum tissues from same patients, and to explore a possible role during carcinogenesis. Methods A high throughput microRNA microarray was performed in human primary medulloblastoma specimens to investigate differentially expressed miRNAs, and some miRNAs were validated using real-time quantitative RT-PCR method. In addition, the predicted target genes for the most significantly downor up-regulated miRNAs were analyzed by using a newly modified ensemble algorithm. Results Nine miRNA species were differentially expressed in medulloblastoma specimens versus normal non-tumorous cerebellum tissues. Of these, 4 were over expressed and 5 were under expressed. The changes ranged from 0.02-fold to 6.61-fold. These findings were confirmed using real-time quantitative RT-PCR for most significant deregulated miRNAs （miR-17, miR-100, miR-106b, and miR-218） which are novel and have not been previously published. Interestingly, most of the predicted target genes for these miRNAs were involved in medulloblastoma carcinogenesis. Conclusions MJRNAs are differentially expressed between human medulloblastoma and non-tumorous cerebellum tissue. MiRNAs may play a role in the tumorigenesis of medulloblastoma and maybe serve as potential targets for novel therapeutic strategies in future.
