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MicroRNA expression signatures determine prognosis and survival in glioblastoma multiforme--a systematic overview.

Henriksen M, Johnsen KB, Andersen HH, Pilgaard L, Duroux M - Mol. Neurobiol. (2014)

Bottom Line: The results are presented with a focus on studies derived from clinical data in databases and independent tissue cohorts where smaller samples sizes were investigated.Here, miRNA associated to longer survival (protective) and miRNA with shorter survival (risk-associated) have been identified and their signatures based on different prognostic attributes are described.Finally, miRNAs associated with disease progression or survival in several studies are identified and functionally described.

View Article: PubMed Central - PubMed

Affiliation: Laboratory for Cancer Biology, Institute of Health Science and Technology, Aalborg University, Fredrik Bajers Vej 3B, 9220, Aalborg Ø, Denmark.

ABSTRACT
Despite advances in our knowledge about glioblastoma multiforme (GBM) pathology, clinical challenges still lie ahead with respect to treatment in GBM due to high prevalence, poor prognosis, and frequent tumor relapse. The implication of microRNAs (miRNAs) in GBM is a rapidly expanding field of research with the aim to develop more targeted molecular therapies. This review aims to present a comprehensive overview of all the available literature, evaluating miRNA signatures as a function of prognosis and survival in GBM. The results are presented with a focus on studies derived from clinical data in databases and independent tissue cohorts where smaller samples sizes were investigated. Here, miRNA associated to longer survival (protective) and miRNA with shorter survival (risk-associated) have been identified and their signatures based on different prognostic attributes are described. Finally, miRNAs associated with disease progression or survival in several studies are identified and functionally described. These miRNAs may be valuable for future determination of patient prognosis and could possibly serve as targets for miRNA-based therapies, which hold a great potential in the treatment of this severe malignant disease.

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Related in: MedlinePlus

The biogenesis of miRNA requires RNA polymerase II/III for the transcription of pri-miRNA. The pri-miRNA product is then cleaved by the Drosha-DGCR8 complex into pre-miRNA. The pre-miRNA is exported to the cytoplasm by Exportin-5 in the presence of Ran-GTP co-factor. Once in the cytoplasm, the pre-miRNA is cleaved by the Dicer-TRBP complex into a miRNA duplex, which is unwound into two products: a guide strand bound to Ago2, which is incorporated into the RISC, and a passenger strand, which is degraded. Finally, the miRNA binds to its target mRNAs resulting in mRNA target cleavage, translational repression, or mRNA decay. A more novel fate of the miRNAs is the selective secretion via microvesicles or exosomes. Ran = Ras-related nuclear protein; GTP = guanosine-5′-triphosphate; TRBP = TAR (HIV-1) RNA binding protein; Ago2 = Argonaute protein 2; RISC = RNA-induced silencing complex
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Fig1: The biogenesis of miRNA requires RNA polymerase II/III for the transcription of pri-miRNA. The pri-miRNA product is then cleaved by the Drosha-DGCR8 complex into pre-miRNA. The pre-miRNA is exported to the cytoplasm by Exportin-5 in the presence of Ran-GTP co-factor. Once in the cytoplasm, the pre-miRNA is cleaved by the Dicer-TRBP complex into a miRNA duplex, which is unwound into two products: a guide strand bound to Ago2, which is incorporated into the RISC, and a passenger strand, which is degraded. Finally, the miRNA binds to its target mRNAs resulting in mRNA target cleavage, translational repression, or mRNA decay. A more novel fate of the miRNAs is the selective secretion via microvesicles or exosomes. Ran = Ras-related nuclear protein; GTP = guanosine-5′-triphosphate; TRBP = TAR (HIV-1) RNA binding protein; Ago2 = Argonaute protein 2; RISC = RNA-induced silencing complex

Mentions: To understand the context of miRNA as a potential prognostic tool in patients with GBM, the essential steps in the biogenesis of miRNAs and the modes by which they exert their repression on downstream targets are summarized (see Fig. 1).Fig. 1


MicroRNA expression signatures determine prognosis and survival in glioblastoma multiforme--a systematic overview.

Henriksen M, Johnsen KB, Andersen HH, Pilgaard L, Duroux M - Mol. Neurobiol. (2014)

The biogenesis of miRNA requires RNA polymerase II/III for the transcription of pri-miRNA. The pri-miRNA product is then cleaved by the Drosha-DGCR8 complex into pre-miRNA. The pre-miRNA is exported to the cytoplasm by Exportin-5 in the presence of Ran-GTP co-factor. Once in the cytoplasm, the pre-miRNA is cleaved by the Dicer-TRBP complex into a miRNA duplex, which is unwound into two products: a guide strand bound to Ago2, which is incorporated into the RISC, and a passenger strand, which is degraded. Finally, the miRNA binds to its target mRNAs resulting in mRNA target cleavage, translational repression, or mRNA decay. A more novel fate of the miRNAs is the selective secretion via microvesicles or exosomes. Ran = Ras-related nuclear protein; GTP = guanosine-5′-triphosphate; TRBP = TAR (HIV-1) RNA binding protein; Ago2 = Argonaute protein 2; RISC = RNA-induced silencing complex
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4225053&req=5

Fig1: The biogenesis of miRNA requires RNA polymerase II/III for the transcription of pri-miRNA. The pri-miRNA product is then cleaved by the Drosha-DGCR8 complex into pre-miRNA. The pre-miRNA is exported to the cytoplasm by Exportin-5 in the presence of Ran-GTP co-factor. Once in the cytoplasm, the pre-miRNA is cleaved by the Dicer-TRBP complex into a miRNA duplex, which is unwound into two products: a guide strand bound to Ago2, which is incorporated into the RISC, and a passenger strand, which is degraded. Finally, the miRNA binds to its target mRNAs resulting in mRNA target cleavage, translational repression, or mRNA decay. A more novel fate of the miRNAs is the selective secretion via microvesicles or exosomes. Ran = Ras-related nuclear protein; GTP = guanosine-5′-triphosphate; TRBP = TAR (HIV-1) RNA binding protein; Ago2 = Argonaute protein 2; RISC = RNA-induced silencing complex
Mentions: To understand the context of miRNA as a potential prognostic tool in patients with GBM, the essential steps in the biogenesis of miRNAs and the modes by which they exert their repression on downstream targets are summarized (see Fig. 1).Fig. 1

Bottom Line: The results are presented with a focus on studies derived from clinical data in databases and independent tissue cohorts where smaller samples sizes were investigated.Here, miRNA associated to longer survival (protective) and miRNA with shorter survival (risk-associated) have been identified and their signatures based on different prognostic attributes are described.Finally, miRNAs associated with disease progression or survival in several studies are identified and functionally described.

View Article: PubMed Central - PubMed

Affiliation: Laboratory for Cancer Biology, Institute of Health Science and Technology, Aalborg University, Fredrik Bajers Vej 3B, 9220, Aalborg Ø, Denmark.

ABSTRACT
Despite advances in our knowledge about glioblastoma multiforme (GBM) pathology, clinical challenges still lie ahead with respect to treatment in GBM due to high prevalence, poor prognosis, and frequent tumor relapse. The implication of microRNAs (miRNAs) in GBM is a rapidly expanding field of research with the aim to develop more targeted molecular therapies. This review aims to present a comprehensive overview of all the available literature, evaluating miRNA signatures as a function of prognosis and survival in GBM. The results are presented with a focus on studies derived from clinical data in databases and independent tissue cohorts where smaller samples sizes were investigated. Here, miRNA associated to longer survival (protective) and miRNA with shorter survival (risk-associated) have been identified and their signatures based on different prognostic attributes are described. Finally, miRNAs associated with disease progression or survival in several studies are identified and functionally described. These miRNAs may be valuable for future determination of patient prognosis and could possibly serve as targets for miRNA-based therapies, which hold a great potential in the treatment of this severe malignant disease.

Show MeSH
Related in: MedlinePlus