Dataset Information

Comparative study of joint bioinformatics analysis of underlying potential of 'neurimmiR', miR-212-3P/miR-132-3P, being involved in epilepsy and its emerging role in human cancer.

ABSTRACT: Considering the critical roles of miR-132/212 participated in central nervous system, many researches started to explored the contributions of miR-132/212 to epilepsy and achieve something worthwhile. Further illuminates all the genes targeted by miR-132/212 may be a valuable means for us to completely understand the working mechanism playing in epilepsy, by which it can influence diverse biological process. This study attempts to establish macrocontrol regulation system and knowledge that miR-212-3p/132-3p effected the epilepsy, for this literature search, miRbase, Vienna RNAfold webserver, Human miRNA tissue atlas, DIANA-TarBase, miRtarbase, STRING, TargetScanhuman, Cytoscape plugin ClueGO + Cluepedia+STRING, DAVID Bioinformatics Resources, Starbase, GeneCards suite and GEO database are comprehensive employed, miR-132-3p/212-3p and its target gene were found have highly expressed in brain and lots of molecular function and metabolic pathways associated with epilepsy may be intervened by it. Meanwhile, the emerging role of miR-132-3p/212-3p being involved in human cancer also been analyzed by several webtools for TCGA data integrative analysis, most remarkably and well worth exploring in our research conclusion that showed miR-132-3p/212-3p may be the core molecular underlying tumor-induced epileptogenesis.

SUBMITTER: Xia L

PROVIDER: S-EPMC5522300 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Comparative study of joint bioinformatics analysis of underlying potential of 'neurimmiR', miR-212-3P/miR-132-3P, being involved in epilepsy and its emerging role in human cancer.

Xia Lu L Li Daojiang D Lin Changwei C Ou Shuchun S Li Xiaorong X Pan Songqing S

Oncotarget 20170601 25

Considering the critical roles of miR-132/212 participated in central nervous system, many researches started to explored the contributions of miR-132/212 to epilepsy and achieve something worthwhile. Further illuminates all the genes targeted by miR-132/212 may be a valuable means for us to completely understand the working mechanism playing in epilepsy, by which it can influence diverse biological process. This study attempts to establish macrocontrol regulation system and knowledge that miR-2 ...[more]

PMID: 28380454

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Project description:It was recently discovered that brain cells release extracellular vesicles (EV) which can pass from brain into blood. These findings raise the possibility that brain-derived EV's present in blood can be used to monitor disease processes occurring in the cerebrum. Since the levels of certain micro-RNAs (miRNAs) have been reported to be altered in Alzheimer's disease (AD) brain, we sought to assess miRNA dysregulation in AD brain tissue and to determine if these changes were reflected in neural EVs isolated from blood of subjects with AD. To this end, we employed high-content miRNA arrays to search for differences in miRNAs in RNA pools from brain tissue of AD (n = 5), high pathological control (HPC) (n = 5), or cognitively intact pathology-free controls (n = 5). Twelve miRNAs were altered by >1.5-fold in AD compared to controls, and six of these were also changed compared to HPCs. Analysis of hits in brain extracts from 11 AD, 7 HPCs and 9 controls revealed a similar fold difference in these six miRNAs, with three showing statistically significant group differences and one with a strong trend toward group differences. Thereafter, we focused on the four miRNAs that showed group differences and measured their content in neurally derived blood EVs isolated from 63 subjects: 16 patients with early stage dementia and a CSF A?42+ tau profile consistent with AD, 16 individuals with mild cognitive impairment (MCI) and an AD CSF profile, and 31 cognitively intact controls with normal CSF A?42+ tau levels. ROC analysis indicated that measurement of miR-132-3p in neurally-derived plasma EVs showed good sensitivity and specificity to diagnose AD, but did not effectively separate individuals with AD-MCI from controls. Moreover, when we measured the levels of a related miRNA, miR-212, we found that this miRNA was also decreased in neural EVs from AD patients compared to controls. Our results suggest that measurement of miR-132 and miR-212 in neural EVs should be further investigated as a diagnostic aid for AD and as a potential theragnostic.

Project description:miR-132 and miR-212 are structurally related microRNAs that have been found to exert powerful modulatory effects within the central nervous system (CNS). Notably, these microRNAs are tandomly processed from the same noncoding transcript, and share a common seed sequence: thus it has been difficult to assess the distinct contribution of each microRNA to gene expression within the CNS. Here, we employed a combination of conditional knockout and transgenic mouse models to examine the contribution of the miR-132/-212 gene locus to learning and memory, and then to assess the distinct effects that each microRNA has on hippocampal gene expression. Using a conditional deletion approach, we show that miR-132/-212 double-knockout mice exhibit significant cognitive deficits in spatial memory, recognition memory, and in tests of novel object recognition. Next, we utilized transgenic miR-132 and miR-212 overexpression mouse lines and the miR-132/-212 double-knockout line to explore the distinct effects of these two miRNAs on the transcriptional profile of the hippocampus. Illumina sequencing revealed that miR-132/-212 deletion increased the expression of 1138 genes; Venn analysis showed that 96 of these genes were also downregulated in mice overexpressing miR-132. Of the 58 genes that were decreased in animals overexpressing miR-212, only four of them were also increased in the knockout line. Functional gene ontology analysis of downregulated genes revealed significant enrichment of genes related to synaptic transmission, neuronal proliferation, and morphogenesis, processes known for their roles in learning, and memory formation. These data, coupled with previous studies, firmly establish a role for the miR-132/-212 gene locus as a key regulator of cognitive capacity. Further, although miR-132 and miR-212 share a seed sequence, these data indicate that these miRNAs do not exhibit strongly overlapping mRNA targeting profiles, thus indicating that these two genes may function in a complex, nonredundant manner to shape the transcriptional profile of the CNS. The dysregulation of miR-132/-212 expression could contribute to signaling mechanisms that are involved in an array of cognitive disorders.

Dataset Information

Comparative study of joint bioinformatics analysis of underlying potential of 'neurimmiR', miR-212-3P/miR-132-3P, being involved in epilepsy and its emerging role in human cancer.

Publications

Comparative study of joint bioinformatics analysis of underlying potential of 'neurimmiR', miR-212-3P/miR-132-3P, being involved in epilepsy and its emerging role in human cancer.

Similar Datasets

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