miR-124 is frequently down-regulated in medulloblastoma and is a negative regulator of SLC16A1

Li, Kay Ka Wai; Pang, Jesse Chung Sean; Ching, Arthur K.; Wong, Chun Kwok; Kong, Xiangyin; Wang, Yin; Zhou, Lei; Chen, Zhongping; Ng, Ho Keung

doi:10.1016/j.humpath.2009.02.003

Cited by 156 publications

(115 citation statements)

References 35 publications

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“…Among these aberrant miRNAs in malignant glioma, miR-124 and miR-128 are better characterized. Together with miR-137, miR-124 inhibits the proliferation of glioblastoma cells by targeting cyclin-dependent kinase 6 (Silber et al, 2008;Li et al, 2009). Strong evidences support that miR-128 act as a tumorigenetic marker of glioma.…”

Section: Discussionmentioning

confidence: 98%

MiR-135a functions as a selective killer of malignant glioma

Lin

et al. 2011

Oncogene

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Glioma is the most common and fatal primary brain tumor. Thus far, therapeutic strategies to efficiently and specifically antagonize glioma are limited and poorly developed. Here we report that glia-enriched miR-135a, a microRNA that is dramatically downregulated in malignant glioma and correlated with the pathological grading, is capable of inducing mitochondria-dependent apoptosis of malignant glioma by regulating various genes including STAT6, SMAD5 and BMPR2, as well as affecting the signaling pathway downstream. Moreover, this lethal effect is selectively towards malignant glioma cells, but not neurons and glial cells, through a novel mechanism. Our findings suggest an important role of miR-135a in glioma etiology and provide a potential candidate for malignant glioma therapy.

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Section: Discussionmentioning

confidence: 98%

MiR-135a functions as a selective killer of malignant glioma

Lin

et al. 2011

Oncogene

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“…The precise role of DICER1 in medulloblastoma is less clear. For example, subsets of miRNAs have been shown as either growth-inhibitory (Ferretti et al 2008;Li et al 2009;Venkataraman et al 2013;Jin et al 2014;Hemmesi et al 2015) or oncogenic (Grunder et al 2011;Weeraratne et al 2012;Li et al 2015). In particular, the miR-1792 cluster has been shown as both necessary and sufficient to initiate medulloblastoma (Zindy et al 2014), which suggests an oncogenic role for Dicer1 on the basis of miR-1792 alone.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA Biogenesis and Hedgehog-Patched Signaling Cooperate to Regulate an Important Developmental Transition in Granule Cell Development

Constantin

Wainwright

2016

Genetics

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The Dicer1, Dcr-1 homolog (Drosophila) gene encodes a type III ribonuclease required for the canonical maturation and functioning of microRNAs (miRNAs). Subsets of miRNAs are known to regulate normal cerebellar granule cell development, in addition to the growth and progression of medulloblastoma, a neoplasm that often originates from granule cell precursors. Multiple independent studies have also demonstrated that deregulation of Sonic Hedgehog (Shh)-Patched (Ptch) signaling, through miRNAs, is causative of granule cell pathologies. In the present study, we investigated the genetic interplay between miRNA biogenesis and Shh-Ptch signaling in granule cells of the cerebellum by way of the Cre/lox recombination system in genetically engineered models of Mus musculus (mouse). We demonstrate that, although the miRNA biogenesis and Shh-Ptch-signaling pathways, respectively, regulate the opposing growth processes of cerebellar hypoplasia and hyperplasia leading to medulloblastoma, their concurrent deregulation was nonadditive and did not bring the growth phenotypes toward an expected equilibrium. Instead, mice developed either hypoplasia or medulloblastoma, but of a greater severity. Furthermore, some genotypes were bistable, whereby subsets of mice developed hypoplasia or medulloblastoma. This implies that miRNAs and Shh-Ptch signaling regulate an important developmental transition in granule cells of the cerebellum. We also conclusively show that the Dicer1 gene encodes a haploinsufficient tumor suppressor gene for Ptch1-induced medulloblastoma, with the monoallielic loss of Dicer1 more severe than biallelic loss. These findings exemplify how genetic interplay between pathways may produce nonadditive effects with a substantial and unpredictable impact on biology. Furthermore, these findings suggest that the functional dosage of Dicer1 may nonadditively influence a wide range of Shh-Ptch-dependent pathologies.

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“…The role of mir-124 in MB development was later confirmed by Li et al who additionally demonstrated that ectopic expression of mir-124 in medulloblastoma cell lines inhibits cell growth by directly targeting SLC16A1, a protein upregulated in MBs, that serve as a carrier to export lactic acid extracellularly, thus maintaining homeostasis of tumor cells, where aerobic glycolysis is known to be accelerated (176).…”

Section: Micrornas In Medulloblastomamentioning

confidence: 85%

Insight into the role of microRNAs in brain tumors (Review)

Catania

Maira²,

Skarmoutsou³

et al. 2011

Int J Oncol

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Abstract. MicroRNAs (MiRNAs) are small non-coding RNAs able to regulate gene expression at a posttranscriptional level. Recent evidence indicates that they play a crucial role in the initiation and progression of human cancers. In this review we briefly describe microRNA biogenesis and function, giving a more detailed account of the current state of knowledge concerning the role of microRNAs in brain tumors and stem-like tumor cells. MicroRNAs control brain tumor development by regulating multiple biological characteristics such as proliferation, invasion, differentiation and angiogenesis. Research in this field is rapidly spreading and encourages potential applications of microRNAs as diagnostic and prognostic tools, in addition to therapeutic targets and tools, to grant clinical benefits to patients suffering of brain tumors. Contents

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miR-124 is frequently down-regulated in medulloblastoma and is a negative regulator of SLC16A1

Cited by 156 publications

References 35 publications

MiR-135a functions as a selective killer of malignant glioma

MiR-135a functions as a selective killer of malignant glioma

MicroRNA Biogenesis and Hedgehog-Patched Signaling Cooperate to Regulate an Important Developmental Transition in Granule Cell Development

Insight into the role of microRNAs in brain tumors (Review)

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