Disrupted microRNA expression caused by Mecp2 loss in a mouse model of Rett syndrome

Urdinguio, Rocío G.; Fernández, Agustín F.; López-Nieva, Pilar; Rossi, Simona; Huertas, Dori; Kulis, Marta; Liu, Chang‐Gong; Croce, Carlo M.; Calin, George A.; Esteller, Manel

doi:10.4161/epi.5.7.13055

Cited by 119 publications

(86 citation statements)

References 59 publications

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“…Other studies have shown differential expression of miR-362-3p in various tissues including the fetal brain of mice, estrogen receptor-positive breast tumors, gastric cancer, and melanoma as well as downregulation of miR-329 in glioma, neuroblastoma, and the mouse model of Rett syndrome. 20,22,29,[33][34][35][36][37][38] The detailed mechanism, however, that governs the differential expression of the two miRs has not been fully elucidated.…”

mentioning

confidence: 99%

“…[41][42][43] Furthermore, MeCP2-deficient mice show altered miR expression, and the latter problem is responsible for the pathogenesis of Rett syndrome. 29,44 MeCP2 is also involved in suppression of miR processing by regulating formation of the DGCR8/Drosha complex in the brain. 45 On the basis of the results from previous studies and our study (data not shown), we believe that upregulation of MeCP2 in breast cancer may result in downregulation of miR-329.…”

mentioning

confidence: 99%

“…Recent studies showed that miR-329 is upregulated in the brain of a mouse model of Rett syndrome; these mice have mutations in the MeCP2 gene, and the MeCP2 level is elevated in neoplastic breast tissues. [27][28][29] To test the possibility that MeCP2 is responsible for the downregulation of miR-329 in breast cancer, we assessed miR-329 expression after transfection of Mecp2 siRNA into MCF7 cells. As shown in Figure 6d, downregulation of MeCP2 resulted in upregulation of miR-329.…”

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confidence: 99%

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Downregulation of microRNA-362-3p and microRNA-329 promotes tumor progression in human breast cancer

Kang

et al. 2015

Cell Death Differ

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p130Cas regulates cancer progression by driving tyrosine receptor kinase signaling. Tight regulation of p130Cas expression is necessary for survival, apoptosis, and maintenance of cell motility in various cell types. Several studies revealed that transcriptional and post-translational control of p130Cas are important for maintenance of its expression and activity. To explore novel regulatory mechanisms of p130Cas expression, we studied the effect of microRNAs (miRs) on p130Cas expression in human breast cancer MCF7 cells. Here, we provide experimental evidence that miR-362-3p and miR-329 perform a tumor-suppressive function and their expression is downregulated in human breast cancer. miR-362-3p and miR-329 inhibited cellular proliferation, migration, and invasion, thereby suppressing tumor growth, by downregulating p130Cas. Ectopic expression of p130Cas attenuated the inhibitory effects of the two miRs on tumor progression. Relative expression levels of miR-362-3p/329 and p130Cas between normal and breast cancer correlated inversely; miR-362-3p/329 expression was decreased, whereas that of p130Cas increased in breast cancers. Furthermore, we showed that downregulation of miR-362-3p and miR-329 was caused by differential DNA methylation of miR genes. Enhanced DNA methylation (according to methylation-specific PCR) was responsible for downregulation of miR-362-3p and miR-329 in breast cancer. Taken together, these findings point to a novel role for miR-362-3p and miR-329 as tumor suppressors; the miR-362-3p/miR-329-p130Cas axis seemingly has a crucial role in breast cancer progression. Thus, modulation of miR-362-3p/miR-329 may be a novel therapeutic strategy against breast cancer. Cell Death and Differentiation (2016) 23, 484-495; doi:10.1038/cdd.2015; published online 4 September 2015 p130Cas/breast cancer anti-estrogen resistance 1 is a member of the Cas (Crk-associated substrate) family of adaptor proteins and has a central role in tyrosine kinasebased signaling related to cell adhesion, migration, cell cycle control, apoptosis, development, and cancer progression.

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confidence: 99%

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confidence: 99%

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Downregulation of microRNA-362-3p and microRNA-329 promotes tumor progression in human breast cancer

Kang

et al. 2015

Cell Death Differ

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“…As the transcriptional process is similar in protein-coding and non-coding genes, and MeCP2 is a transcriptional regulator, it is likely that the transcription of non-coding RNAs is regulated by MeCP2. As expected, deletion of Mecp2 results in disrupted expression of miRNAs and lncRNAs in the mouse model of RTT [43][44][45] .…”

Section: Gene Expression Regulated By Mecp2: From Mrnas To Non-codingmentioning

confidence: 89%

“…Then, further studies analyzed the expression profi les of miRNAs in the whole brain or cerebellum of Mecp2-null mice and found that the levels of many miRNAs were altered [43,44] .…”

Section: Modulation Of Gene Expression At the Post-mentioning

confidence: 99%

MeCP2: multifaceted roles in gene regulation and neural development

Cheng

Qiu

2014

Neurosci. Bull.

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Methyl-CpG-binding protein 2 (MeCP2) is a classic methylated-DNA-binding protein, dysfunctions of which lead to various neurodevelopmental disorders such as Rett syndrome and autism spectrum disorder. Initially recognized as a transcriptional repressor, MeCP2 has been studied extensively and its functions have been expanded dramatically in the past two decades. Recently, it was found to be involved in gene regulation at the post-transcriptional level. MeCP2 represses nuclear microRNA processing by interacting directly with the Drosha/DGCR8 complex. In addition to its multifaceted functions, MeCP2 is remarkably modulated by posttranslational modifi cations such as phosphorylation, SUMOylation, and acetylation, providing more regulatory dimensions to its functions. The role of MeCP2 in the central nervous system has been studied extensively, from neurons to glia. Future investigations combining molecular, cellular, and physiological methods are necessary for defi ning the roles of MeCP2 in the brain and developing effi cient treatments for MeCP2-related brain disorders.

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Role of microRNAs in Autism Spectrum Disorder

Sarachana

2013

microRNAs in Toxicology and Medicine

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Disrupted microRNA expression caused by Mecp2 loss in a mouse model of Rett syndrome

Cited by 119 publications

References 59 publications

Downregulation of microRNA-362-3p and microRNA-329 promotes tumor progression in human breast cancer

Downregulation of microRNA-362-3p and microRNA-329 promotes tumor progression in human breast cancer

MeCP2: multifaceted roles in gene regulation and neural development

Role of microRNAs in Autism Spectrum Disorder

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