MicroRNA-34a activation in tuberous sclerosis complex during early brain development may lead to impaired corticogenesis

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064203%3A_____%2F21%3A10427358" target="_blank" >RIV/00064203:_____/21:10427358 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11130/21:10427358

Result on the web

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=fr16ZtgVTv" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=fr16ZtgVTv</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1111/nan.12717" target="_blank" >10.1111/nan.12717</a>

Result language

angličtina

Original language name

MicroRNA-34a activation in tuberous sclerosis complex during early brain development may lead to impaired corticogenesis

Original language description

AIMS: Tuberous sclerosis complex (TSC) is a genetic disorder associated with dysregulation of the mechanistic target of rapamycin complex 1 (mTORC1) signalling pathway. Neurodevelopmental disorders, frequently present in TSC, are linked to cortical tubers in the brain. We previously reported microRNA-34a (miR-34a) among the most up-regulated miRs in tubers. Here, we characterized miR-34a expression in tubers with the focus on the early brain development and assessed the regulation of mTORC1 pathway and corticogenesis by miR-34a. METHODS: We analysed the expression of miR-34a in resected cortical tubers (n = 37) compared to autopsy-derived control tissue (n = 27). The effect of miR-34a overexpression on corticogenesis was assessed in mice at E18. The regulation of the mTORC1 pathway and the expression of the bioinformatically predicted target genes were assessed in primary astrocyte cultures from 3 patients with TSC and in SH-SY5Y cells following miR-34a transfection. RESULTS: The peak of miR-34a overexpression in tubers was observed during infancy, concomitant with the presence of pathological markers, particularly in giant cells and dysmorphic neurons. MiR-34a was also strongly expressed in fetal TSC cortex. Overexpression of miR-34a in mouse embryos decreased the percentage of cells migrated to the cortical plate. The transfection of miR-34a mimic in TSC astrocytes negatively regulated mTORC1 and decreased the expression of the target genes RAS related (RRAS) and NOTCH1. CONCLUSIONS: MiR-34a is most highly overexpressed in tubers during fetal and early postnatal brain development. MiR-34a can negatively regulate mTORC1, however, it may also contribute to abnormal corticogenesis in TSC.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30103 - Neurosciences (including psychophysiology)

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2021

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Neuropathology and Applied Neurobiology

ISSN

0305-1846

e-ISSN

—

Volume of the periodical

47

Issue of the periodical within the volume

6

Country of publishing house

GB - UNITED KINGDOM

Number of pages

16

Pages from-to

796-811

UT code for WoS article

000661128000001

EID of the result in the Scopus database

2-s2.0-85107727171