Circadian gene Clock contributes to cell proliferation and migration of glioma and is directly regulated by tumor‐suppressive miR‐124

Li, Aihua; Lin, Xihua; Tan, Xiaochao; Yin, Bin; Han, Wei; Zhao, Jizong; Yuan, Jing; Qiang, Boqin; Peng, Xiaozhong

doi:10.1016/j.febslet.2013.06.018

Cited by 71 publications

(67 citation statements)

References 37 publications

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“…Although some studies indicate that specific clock genes may act as tumor suppressors (Fu et al, 2002), other studies suggest a more complex relationship between the circadian rhythm and cancer (Antoch et al, 2013). Our finding that AML cells require Clock and Bmal1 expression reinforces recent work demonstrating tumor-maintaining roles for the core circadian rhythm genes in a variety of cancers (Antoch et al, 2008; Cui et al, 2015; Elshazley et al, 2012; Janich et al, 2011; Li et al, 2013; Ozturk et al, 2009; Xiao et al, 2014). …”

Section: Discussionsupporting

confidence: 88%

Core Circadian Clock Genes Regulate Leukemia Stem Cells in AML

Puram

Kowalczyk

Boer

et al. 2016

Cell

220

205

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SUMMARY Leukemia stem cells (LSCs) have the capacity to self-renew and propagate disease upon serial transplantation in animal models, and elimination of this cell population is required for curative therapies. Here, we describe a series of pooled, in vivo RNA interference (RNAi) screens to identify essential transcription factors (TFs) in a murine model of acute myeloid leukemia (AML) with genetically- and phenotypically-defined LSCs. These screens reveal the heterodimeric, circadian rhythm TFs Clock and Bmal1 as genes required for the growth of AML cells in vitro and in vivo. Disruption of canonical circadian pathway components produces anti-leukemic effects, including impaired proliferation, enhanced myeloid differentiation, and depletion of LSCs. We find that both normal and malignant hematopoietic cells harbor an intact clock with robust circadian oscillations, and genetic knockout models reveal a leukemia-specific dependence on the pathway. Our findings establish a role for the core circadian clock genes in AML.

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Section: Discussionsupporting

confidence: 88%

Core Circadian Clock Genes Regulate Leukemia Stem Cells in AML

Puram

Kowalczyk

Boer

et al. 2016

Cell

220

205

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“…Interestingly, it appears that circadian genes are to some extent related to glioma risk and outcome [66]. In particular elevated levels of CLOCK contribute to cell proliferation and migration in glioma [67]. Of note is that Clock is directly regulated by REV-ERBα [45] and therefore agonists for REV-ERBα [4] may not only reduce Fabp7 expression but also Clock levels, which may reduce neurogenesis and lower the potential of glioblastoma development.…”

Section: Discussionmentioning

confidence: 99%

The Nuclear Receptor REV-ERBα Regulates Fabp7 and Modulates Adult Hippocampal Neurogenesis

et al. 2014

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The function of the nuclear receptor Rev-erbα (Nr1d1) in the brain is, apart from its role in the circadian clock mechanism, unknown. Therefore, we compared gene expression profiles in the brain between wild-type and Rev-erbα knock-out (KO) animals. We identified fatty acid binding protein 7 (Fabp7, Blbp) as a direct target of repression by REV-ERBα. Loss of Rev-erbα manifested in memory and mood related behavioral phenotypes and led to overexpression of Fabp7 in various brain areas including the subgranular zone (SGZ) of the hippocampus, where neuronal progenitor cells (NPCs) can initiate adult neurogenesis. We found increased proliferation of hippocampal neurons and loss of its diurnal pattern in Rev-erbα KO mice. In vitro, proliferation and migration of glioblastoma cells were affected by manipulating either Fabp7 expression or REV-ERBα activity. These results suggest an important role of Rev-erbα and Fabp7 in adult neurogenesis, which may open new avenues for treatment of gliomas as well as neurological diseases such as depression and Alzheimer.

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“…Many miRNAs have been proved to be proto-oncogenes or tumor suppressors in various human cancers, including in glioma. [3][4][5] Recent studies have revealed that miRNAs, such as miR-7, 6, 7 miR-124, [8][9][10] miR-128, 11 miR-107, 12 and miR-181b, [13][14][15] are globally dysregulated in glioma. However, the particular molecular mechanisms through which miRNAs mediate glioma carcinogenesis and metastasis are still largely unknown.…”

Section: Introductionmentioning

confidence: 99%

MiR-302c-3p suppresses invasion and proliferation of glioma cells via down-regulating metadherin (MTDH) expression

Wang

Wei

Tong

et al. 2015

Cancer Biology & Therapy

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Glioma is the most common malignant brain tumors with poor prognosis. The molecular events involved in the development and progression of glioma remain unclear. In this study, the expression levels of miR-302c-3p were examined in glioma tissues by qRT-PCR. The in vitro and in vivo functional effects of miR-302c-3p were examined further. Luciferase reporter assays were conducted to confirm the targeting associations. Results showed that the expression level of miR-302c-3p in glioma tissues was significantly lower than those in normal brain tissues (P < 0.001). The decreased expression of mi-302c-3p in glioma was positively associated with WHO grade (P < 0.001). Up-regulation of MTDH was also detected in glioma tumors compared with normal brain tissues (P = 0.0027) and is inversely correlated with miR-302c-3p expression (P = 0.003, R(2) = 0.4065). MTDH mRNA is a direct target of miR-302c-3p, whose ectopic expression decreases MTDH expression through binding to its 3'-untranslated region. Overexpression of miR-302c-3p results in a dramatic inhibition of glioma cells proliferation and invasion in vitro and in vivo. These data suggest that miR-302c-3p play a pivotal role in the progression of glioma by targeting MTDH and is a potential inhibitor in glioma treatment.

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Circadian gene Clock contributes to cell proliferation and migration of glioma and is directly regulated by tumor‐suppressive miR‐124

Cited by 71 publications

References 37 publications

Core Circadian Clock Genes Regulate Leukemia Stem Cells in AML

Core Circadian Clock Genes Regulate Leukemia Stem Cells in AML

The Nuclear Receptor REV-ERBα Regulates Fabp7 and Modulates Adult Hippocampal Neurogenesis

MiR-302c-3p suppresses invasion and proliferation of glioma cells via down-regulating metadherin (MTDH) expression

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