The microRNA miR-34 modulates ageing and neurodegeneration in Drosophila

Liu, Nan; Landreh, Michael; Cao, Kajia; Abe, Masashi; Hendriks, Gert‐Jan; Kennerdell, Jason R.; Zhu, Yongqing; Wang, Li-San; Bonini, Nancy M.

doi:10.1038/nature10810

Cited by 352 publications

(375 citation statements)

References 34 publications

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“…An age‐associated alteration in miR‐34 occurs in the mouse and overexpression of miR‐34 in Drosophila extends lifespan (Li et al ., 2011; Liu et al ., 2012). miR‐34 may play an important role in responding to DNA damage and also in protecting against osteoporosis and neurodegeneration (Kato et al ., 2009; Liu et al ., 2012; Krzeszinski et al ., 2014). Metformin has been shown to upregulate miR‐34a in cancer cells in culture (Do et al ., 2014).…”

Section: Discussionmentioning

confidence: 99%

Metformin‐mediated increase in DICER1 regulates microRNA expression and cellular senescence

et al. 2016

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SummaryMetformin, an oral hypoglycemic agent, has been used for decades to treat type 2 diabetes mellitus. Recent studies indicate that mice treated with metformin live longer and have fewer manifestations of age‐related chronic disease. However, the molecular mechanisms underlying this phenotype are unknown. Here, we show that metformin treatment increases the levels of the microRNA‐processing protein DICER1 in mice and in humans with diabetes mellitus. Our results indicate that metformin upregulates DICER1 through a post‐transcriptional mechanism involving the RNA‐binding protein AUF1. Treatment with metformin altered the subcellular localization of AUF1, disrupting its interaction with DICER1 mRNA and rendering DICER1 mRNA stable, allowing DICER1 to accumulate. Consistent with the role of DICER1 in the biogenesis of microRNAs, we found differential patterns of microRNA expression in mice treated with metformin or caloric restriction, two proven life‐extending interventions. Interestingly, several microRNAs previously associated with senescence and aging, including miR‐20a, miR‐34a, miR‐130a, miR‐106b, miR‐125, and let‐7c, were found elevated. In agreement with these findings, treatment with metformin decreased cellular senescence in several senescence models in a DICER1‐dependent manner. Metformin lowered p16 and p21 protein levels and the abundance of inflammatory cytokines and oncogenes that are hallmarks of the senescence‐associated secretory phenotype (SASP). These data lead us to hypothesize that changes in DICER1 levels may be important for organismal aging and to propose that interventions that upregulate DICER1 expression (e.g., metformin) may offer new pharmacotherapeutic approaches for age‐related disease.

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Section: Discussionmentioning

confidence: 99%

Metformin‐mediated increase in DICER1 regulates microRNA expression and cellular senescence

et al. 2016

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“…MicroRNAs modulate protein expression by binding to the 3'UTR of mRNA and promoting RNA degradation, inhibiting mRNA translation, and affecting transcription (9)(10)(11)(12). The miR-7 gene is found in most sequenced urbilateria species, and the sequence of its mature miRNA product is perfectly conserved from annelids to humans, indicating strong functional conservation (13)(14)(15).…”

Section: Introductionmentioning

confidence: 99%

miR-7 inhibits glioblastoma growth by simultaneously interfering with the PI3K/ATK and Raf/MEK/ERK pathways

Liu

Jiang

Huang

et al. 2014

International Journal of Oncology

126

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Abstract. Epidermal growth factor receptor (EGFR) signaling regulates glioblastoma cell proliferation, survival, migration and invasion and plays a key role in tumor progression. We show that microRNA-7 (miR-7) is a common regulator of the phosphoinositide-3-kinase (PI3K)/ATK and Raf/ mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathways, both of which are launched by EGFR through its two direct targets, the transcription factors PI3K and Raf-1, respectively. Enforced expression of miR-7 markedly decreased expression of PI3K, phosphorylated Akt, Raf-1, phosphorylated MEK 1/2, and cyclin D1, as well as slightly reduced expression of EGFR. Forced expression of PI3K or Raf-1 transcripts lacking the 3'-untranslated region (3'-UTR) partially reversed the effects of miR-7 on cell growth inhibition and cell cycle arrest in glioma cells. Additionally, transient expression of miR-7 in glioblastoma cells strongly inhibited in vivo glioblastoma xenograft growth. We conclude that miR-7 is a potential tumor suppressor in glioblastoma that acts by targeting multiple oncogenes related to the downstream pathway of EGFR and may serve as a novel therapeutic target for malignant gliomas.

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“…Given its neurobiological role, decreased levels of BC200 likely influence age-associated changes in synaptic functioning. It is intriguing to speculate that lncRNAs-like miRNAs-may be responsible for brain aging, rather than simply being markers thereof [69].…”

Section: Brain Agingmentioning

confidence: 99%

Long Non-coding RNAs: Novel Targets for Nervous System Disease Diagnosis and Therapy

2013

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The human genome encodes tens of thousands of long non-coding RNAs (lncRNAs), a novel and important class of genes. Our knowledge of lncRNAs has grown exponentially since their discovery within the last decade. lncRNAs are expressed in a highly cell-and tissue-specific manner, and are particularly abundant within the nervous system. lncRNAs are subject to post-transcriptional processing and inter-and intra-cellular transport. lncRNAs act via a spectrum of molecular mechanisms leveraging their ability to engage in both sequence-specific and conformational interactions with diverse partners (DNA, RNA, and proteins). Because of their size, lncRNAs act in a modular fashion, bringing different macromolecules together within the three-dimensional context of the cell. lncRNAs thus coordinate the execution of transcriptional, post-transcriptional, and epigenetic processes and critical biological programs (growth and development, establishment of cell identity, and deployment of stress responses). Emerging data reveal that lncRNAs play vital roles in mediating the developmental complexity, cellular diversity, and activitydependent plasticity that are hallmarks of brain. Corresponding studies implicate these factors in brain aging and the pathophysiology of brain disorders, through evolving paradigms including the following: (i) genetic variation in lncRNA genes causes disease and influences susceptibility; (ii) epigenetic deregulation of lncRNAs genes is associated with disease; (iii) genomic context links lncRNA genes to disease genes and pathways; and (iv) lncRNAs are otherwise interconnected with known pathogenic mechanisms. Hence, Electronic supplementary material The online version of this article

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The microRNA miR-34 modulates ageing and neurodegeneration in Drosophila

Cited by 352 publications

References 34 publications

Metformin‐mediated increase in DICER1 regulates microRNA expression and cellular senescence

Metformin‐mediated increase in DICER1 regulates microRNA expression and cellular senescence

miR-7 inhibits glioblastoma growth by simultaneously interfering with the PI3K/ATK and Raf/MEK/ERK pathways

Long Non-coding RNAs: Novel Targets for Nervous System Disease Diagnosis and Therapy

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