Meta-coexpression conservation analysis of microarray data: a "subset" approach provides insight into brain-derived neurotrophic factor regulation

Aid-Pavlidis, Tamara; Pavlidis, Pavlos; Timmusk, Tõnis

doi:10.1186/1471-2164-10-420

Cited by 14 publications

(11 citation statements)

References 110 publications

(143 reference statements)

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“…BDNF belongs to the neurotrophin superfamily of polypeptide growth factors and plays important roles in neuronal survival, neurogenesis, differentiation and neurite growth throughout the central nervous system [32] . Moreover BDNF has been associated with various human diseases including depression, epilepsy, Alzheimer, Parkinson and Huntington [33] , [34] , i.e. BDNF has been mainly studied as a growth factor in the central and peripheral nervous system.…”

Section: Discussionmentioning

confidence: 99%

BDNF Is Associated with SFRP1 Expression in Luminal and Basal-Like Breast Cancer Cell Lines and Primary Breast Cancer Tissues: A Novel Role in Tumor Suppression?

et al. 2014

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Secreted frizzled related protein 1 (SFRP1) functions as an important inhibitor of the Wnt pathway and is a known tumor suppressor gene, which is epigenetically silenced in a variety of tumors e.g. in breast cancer. However, it is still unclear how SFRP1 exactly affects the Wnt pathway. Our aim was to decipher SFRP1 involvement in biochemical signaling in dependency of different breast cancer subtypes and to identify novel SFRP1-regulated genes. We generated SFRP1 over-expressing in vitro breast cancer models, reflecting the two major subtypes by using basal-like BT20 and luminal-like HER2-positive SKBR3 cells. DNA microarray expression profiling of these models revealed that SFRP1 expression potentially modulates Bone morphogenetic protein- and Smoothened signaling (p<0.01), in addition to the known impact on Wnt signaling. Importantly, further statistical analysis revealed that in dependency of the cancer subtype model SFRP1 may affect the canonical and non-canonical Wnt pathway (p<0.01), respectively. While SFRP1 re-expression generally mediated distinct patterns of transcriptionally induced or repressed genes in BT20 and SKBR3 cells, brain derived neurotrophic factor (BDNF) was identified as a SFRP1 induced gene in both cell lines. Although BDNF has been postulated as a putative oncogene, the co-regulation with SFRP1 indicates a potential suppressive function in breast cancer. Indeed, a positive correlation between SFRP1 and BDNF protein expression could be shown (p<0.001) in primary breast cancer samples. Moreover, TCGA dataset based analysis clearly underscores that BDNF mRNA is down-regulated in primary breast cancer samples predicting a poor prognosis of these patients. In line, we functionally provide evidence that stable BDNF re-expression in basal-like BT20 breast cancer cells blocks tumor cell proliferation. Hence, our results suggest that BDNF might rather mediate suppressive than promoting function in human breast cancer whose mode of action should be addressed in future studies.

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Section: Discussionmentioning

confidence: 99%

BDNF Is Associated with SFRP1 Expression in Luminal and Basal-Like Breast Cancer Cell Lines and Primary Breast Cancer Tissues: A Novel Role in Tumor Suppression?

et al. 2014

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“…The developmental, regional, and conditional patterns in which a gene is expressed may contribute to the identification of TFs involved in regulating target genes (Aid-Pavlidis et al 2009;Schena et al 1995). On the basis of our own previous investigations and those of others we selected experimental conditions known to increase or decrease prestin expression: (i) prestin expression increases during the early postnatal period; (ii) prestin expression can be modulated in organotypic cultures by changing the culture medium.…”

Section: Introductionmentioning

confidence: 99%

Expression Analysis of Prestin and Selected Transcription Factors in Newborn Rats

et al. 2011

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Transcription factors (TFs) have a central role to play in regulating gene expression. To analyze the co-expression patterns of selected TFs with the motor protein prestin of the outer hair cells, we applied an real-time PCR approach combining several kinds of information: (i) expression changes during postnatal development, (ii) expression changes by exposure of organotypic cultures of the organ of Corti to factors which significantly affect prestin expression [thyroid hormone (T4), retinoic acid (RA), butyric acid (BA), increased KCl concentration] and (iii) changes along the apical-basal gradient. We found that the mRNA levels of the TF Brn-3c (Pou4f3), a member of the POU family, are significantly associated with the regulation of prestin during postnatal development and in cultures supplemented with T4 (0.5 μM), BA (0.5-2.0 mM), and high KCl (50 mM) concentration. The mRNA level of the constitutively active TF C/ebpb (CCAAT/enhancer binding protein beta) correlates positively with the prestin expression during postnatal development and in cultures exposed to T4 and RA (50-100 μM). The mRNA levels of the calcium-dependent TF CaRF correlates significantly with the prestin expression in cultures exposed to T4 and high KCl concentration. The observed coexpression patterns may suggest that the TFs Brn-3c, C/ebpb, and Carf contribute to regulating the expression of prestin under the investigated conditions.

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“…It is noteworthy here that miR-23a, another candidate microRNA, is also induced by long-term potentiation with implications in memory consolidation [88]. More importantly, brain expressions of BDNF connected to behavioral activation of dopaminergic neurons showed positive correlation with that of SNCA [89,90], the candidate gene up-regulated in the high COMB and high Edu groups after music-24 listening [10] and in musicians after music-performance [11]. Furthermore, SNCA also activates BDNF [91] and BDNF and SNCA are regulated by GATA2, which is located in the strongest associated region for musical aptitude [8,10].…”

Section: Discussionmentioning

confidence: 71%

Music-listening regulates human microRNA transcriptome

Raijas

Ahvenainen

et al. 2019

Preprint

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Here, we used microRNA sequencing to study the effect of 20 minutes of classical musiclistening on the peripheral blood microRNA transcriptome in subjects characterized for musical aptitude and music education and compared it to a control study without music for the same duration. In participants with high musical aptitude, we identified up-regulation of six microRNAs (hsa-miR-132-3p, hsa-miR-361-5p, hsa-miR-421, hsa-miR-23a-3p, hsa-miR-23b-3p, hsa-miR-25-3p) and down-regulation of two microRNAs (hsa-miR-378a-3p, hsa-miR-16-2-3p) post music-listening. The up-regulated microRNAs were found to be regulators of neuron apoptosis and neurotoxicity, consistent with previously reported neuroprotective role of music.Some up-regulated microRNAs were reported to be responsive to neuronal activity (miR-132, miR-23a, miR-23b) and modulators of neuronal plasticity, CNS myelination and cognitive functions like long-term potentiation and memory. miR-132 and DICER, up-regulated after music-listening, protect dopaminergic neurons and is important for retaining striatal dopamine levels. miR-23 putatively activates pro-survival PI3K/AKT signaling cascade, which is coupled with dopaminergic signaling. Some of the transcriptional regulators (FOS, CREB1, JUN, EGR1 and BDNF) of the up-regulated microRNAs are sensory-motor stimuli induced immediate early genes and top candidates associated with musical traits. Amongst these, BDNF is co-expressed with SNCA, up-regulated in music-listening and music-performance, and both are activated by GATA2, which is associated with musical aptitude. Some of the candidate microRNAs and their putative regulatory interactions were previously identified to be associated with song-learning, singing and seasonal plasticity networks in songbirds and imply evolutionary conservation of the auditory perception process: miR-23a, miR-23b and miR-25 repress PTEN and indirectly 3 activates the MAPK signaling pathway, a regulator of neuronal plasticity which is activated after song-listening. We did not detect any significant changes in microRNA expressions associated with music education or low musical aptitude. Our data thereby show the importance of inherent musical aptitude for music appreciation and for eliciting the human microRNA response to music-listening.

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Meta-coexpression conservation analysis of microarray data: a "subset" approach provides insight into brain-derived neurotrophic factor regulation

Cited by 14 publications

References 110 publications

BDNF Is Associated with SFRP1 Expression in Luminal and Basal-Like Breast Cancer Cell Lines and Primary Breast Cancer Tissues: A Novel Role in Tumor Suppression?

BDNF Is Associated with SFRP1 Expression in Luminal and Basal-Like Breast Cancer Cell Lines and Primary Breast Cancer Tissues: A Novel Role in Tumor Suppression?

Expression Analysis of Prestin and Selected Transcription Factors in Newborn Rats

Music-listening regulates human microRNA transcriptome

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