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Epigenetic dysregulation in glioma.

Kondo Y, Katsushima K, Ohka F, Natsume A, Shinjo K - Cancer Sci. (2014)

Bottom Line: Recent genome-wide genomic and epigenomic analyses have revealed that mutations in epigenetic modifiers occur frequently in gliomas and that dysregulation of epigenetic mechanisms is closely associated with glioma formation.Given that epigenetic changes are reversible, understanding the epigenetic abnormalities that arise in gliomagenesis might be key to developing more effective treatment strategies for glioma.In this review, we focus on the recent advancements in epigenetic research with respect to gliomas, consider how epigenetic mechanisms dynamically regulate tumor cells, including the cancer stem cell population, and discuss perspectives and challenges for glioma treatment in the near future.

View Article: PubMed Central - PubMed

ABSTRACT
Given that treatment options for patients with glioblastoma are limited, much effort has been made to clarify the underlying mechanisms of gliomagenesis. Recent genome-wide genomic and epigenomic analyses have revealed that mutations in epigenetic modifiers occur frequently in gliomas and that dysregulation of epigenetic mechanisms is closely associated with glioma formation. Given that epigenetic changes are reversible, understanding the epigenetic abnormalities that arise in gliomagenesis might be key to developing more effective treatment strategies for glioma. In this review, we focus on the recent advancements in epigenetic research with respect to gliomas, consider how epigenetic mechanisms dynamically regulate tumor cells, including the cancer stem cell population, and discuss perspectives and challenges for glioma treatment in the near future.

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miRNA associated with the maintenance of glioma stem cells (GSC). miR-9/9*, the miR17-92 cluster, and miR-1275 are upregulated in GSC. Targets of these miRNA, namely calmodulin-binding transcription activator 1 (CAMTA1), connective tissue growth factor (CTGF) and CLDN11, act as tumor suppressors. In contrast, miR-34a, miR-128, miR-124 and miR-137 are downregulated in GSC. miR-34a inhibits the expression of Notch1 and Notch2, which are receptors of notch signaling molecules. miR-128 inhibits GSC self-renewal by directly targeting BMI1 and SUZ12, components of PRC1 and PRC2, respectively. miR-124 and miR-137 induce G0/G1 cell cycle arrest by targeting cyclin-dependent kinase 6 (CDK6).
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fig04: miRNA associated with the maintenance of glioma stem cells (GSC). miR-9/9*, the miR17-92 cluster, and miR-1275 are upregulated in GSC. Targets of these miRNA, namely calmodulin-binding transcription activator 1 (CAMTA1), connective tissue growth factor (CTGF) and CLDN11, act as tumor suppressors. In contrast, miR-34a, miR-128, miR-124 and miR-137 are downregulated in GSC. miR-34a inhibits the expression of Notch1 and Notch2, which are receptors of notch signaling molecules. miR-128 inhibits GSC self-renewal by directly targeting BMI1 and SUZ12, components of PRC1 and PRC2, respectively. miR-124 and miR-137 induce G0/G1 cell cycle arrest by targeting cyclin-dependent kinase 6 (CDK6).

Mentions: Studies have shown that miRNA play an important regulatory role during tumor formation in GBM.(49,52–54,58) miR-9/9* is highly abundant in CD133+ cells and inhibition of miR-9/9* leads to reduced formation of neurospheres (Fig. 4).(49) Conceivably, CD133 is a stem cell marker that might be able to distinguish the small subpopulations of cancer cells with strong tumorigenic activity that are found in some GBM.(50) However, recent reports, including ours, suggest that expression of CD133 is a feature of GSC rather than a defined marker that distinguishes cells at different hierarchical levels in tumors.(36,51) The robustness of some markers of cancer stem cells remains to be determined.


Epigenetic dysregulation in glioma.

Kondo Y, Katsushima K, Ohka F, Natsume A, Shinjo K - Cancer Sci. (2014)

miRNA associated with the maintenance of glioma stem cells (GSC). miR-9/9*, the miR17-92 cluster, and miR-1275 are upregulated in GSC. Targets of these miRNA, namely calmodulin-binding transcription activator 1 (CAMTA1), connective tissue growth factor (CTGF) and CLDN11, act as tumor suppressors. In contrast, miR-34a, miR-128, miR-124 and miR-137 are downregulated in GSC. miR-34a inhibits the expression of Notch1 and Notch2, which are receptors of notch signaling molecules. miR-128 inhibits GSC self-renewal by directly targeting BMI1 and SUZ12, components of PRC1 and PRC2, respectively. miR-124 and miR-137 induce G0/G1 cell cycle arrest by targeting cyclin-dependent kinase 6 (CDK6).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4317798&req=5

fig04: miRNA associated with the maintenance of glioma stem cells (GSC). miR-9/9*, the miR17-92 cluster, and miR-1275 are upregulated in GSC. Targets of these miRNA, namely calmodulin-binding transcription activator 1 (CAMTA1), connective tissue growth factor (CTGF) and CLDN11, act as tumor suppressors. In contrast, miR-34a, miR-128, miR-124 and miR-137 are downregulated in GSC. miR-34a inhibits the expression of Notch1 and Notch2, which are receptors of notch signaling molecules. miR-128 inhibits GSC self-renewal by directly targeting BMI1 and SUZ12, components of PRC1 and PRC2, respectively. miR-124 and miR-137 induce G0/G1 cell cycle arrest by targeting cyclin-dependent kinase 6 (CDK6).
Mentions: Studies have shown that miRNA play an important regulatory role during tumor formation in GBM.(49,52–54,58) miR-9/9* is highly abundant in CD133+ cells and inhibition of miR-9/9* leads to reduced formation of neurospheres (Fig. 4).(49) Conceivably, CD133 is a stem cell marker that might be able to distinguish the small subpopulations of cancer cells with strong tumorigenic activity that are found in some GBM.(50) However, recent reports, including ours, suggest that expression of CD133 is a feature of GSC rather than a defined marker that distinguishes cells at different hierarchical levels in tumors.(36,51) The robustness of some markers of cancer stem cells remains to be determined.

Bottom Line: Recent genome-wide genomic and epigenomic analyses have revealed that mutations in epigenetic modifiers occur frequently in gliomas and that dysregulation of epigenetic mechanisms is closely associated with glioma formation.Given that epigenetic changes are reversible, understanding the epigenetic abnormalities that arise in gliomagenesis might be key to developing more effective treatment strategies for glioma.In this review, we focus on the recent advancements in epigenetic research with respect to gliomas, consider how epigenetic mechanisms dynamically regulate tumor cells, including the cancer stem cell population, and discuss perspectives and challenges for glioma treatment in the near future.

View Article: PubMed Central - PubMed

ABSTRACT
Given that treatment options for patients with glioblastoma are limited, much effort has been made to clarify the underlying mechanisms of gliomagenesis. Recent genome-wide genomic and epigenomic analyses have revealed that mutations in epigenetic modifiers occur frequently in gliomas and that dysregulation of epigenetic mechanisms is closely associated with glioma formation. Given that epigenetic changes are reversible, understanding the epigenetic abnormalities that arise in gliomagenesis might be key to developing more effective treatment strategies for glioma. In this review, we focus on the recent advancements in epigenetic research with respect to gliomas, consider how epigenetic mechanisms dynamically regulate tumor cells, including the cancer stem cell population, and discuss perspectives and challenges for glioma treatment in the near future.

Show MeSH
Related in: MedlinePlus