Quantitative and integrated proteome and microRNA analysis of endothelial replicative senescence

Yentrapalli, Ramesh; Azimzadeh, Omid; Kraemer, Anne; Malinowsky, Katharina; Sarioglu, Hakan; Becker, Karl‐Friedrich; Atkinson, Michael J.; Moertl, Simone; Tapio, Soile

doi:10.1016/j.jprot.2015.05.023

Cited by 25 publications

(14 citation statements)

References 77 publications

(89 reference statements)

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“…MiR-16-5p and miR-223-3p are widely studied in different cellular models. Age-related changes of miR-16-5p have been shown to be associated with vascular and neurodegenerative diseases and B-cell function [ 38 , 39 ] whereas, with advanced age, an increase of miR-223-3p in inflammatory cells has been reported [ 40 ]. MiR-223-3p was also found to regulate macrophage activation resulting in the suppression of pro-inflammatory responses in the adipose tissue of mice [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

Menopause and adipose tissue: miR-19a-3p is sensitive to hormonal replacement

et al. 2017

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Tissue-specific effects of 17β-estradiol are delivered via both estrogen receptors and microRNAs (miRs). Menopause is known to affect the whole-body fat distribution in women. This investigation aimed at identifying menopause- and hormone replacement therapy (HRT)-associated miR profiles and miR targets in subcutaneous abdominal adipose tissue and serum from the same women. A discovery phase using array technology was performed in 13 women, including monozygotic twin pairs discordant for HRT and premenopausal young controls. Seven miRs, expressed in both adipose tissue and serum, were selected for validation phase in 34 women from a different cohort. An age/menopause-related increase of miRs-16-5p, -451a, -223-3p, -18a-5p, -19a-3p,-486-5p and -363-3p was found in the adipose tissue, but not in serum. MiR-19a-3p, involved in adipocyte development and estrogen signaling, resulted to be higher in HRT users in comparison with non-users. Among the identified targets, AKT1, BCL-2 and BRAF proteins showed lower expression in both HRT and No HRT users in comparison with premenopausal women. Unexpectedly, ESR1 protein expression was not modified although its mRNA was lower in No HRT users compared to premenopausal women and HRT users. Thus, both HRT and menopause appear to affect adipose tissue homeostasis via miR-mediated mechanism.

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Section: Discussionmentioning

confidence: 99%

Menopause and adipose tissue: miR-19a-3p is sensitive to hormonal replacement

et al. 2017

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“…The serum miR-376a-3p was significantly diminished in obese serum and could serve as a potential predictive tool for distinguishing obese patients from normal healthy controls [ 17 ]. miR-376a-3p was associated with the senescence of human umbilical vein endothelial cells (HUVEC) [ 23 ]. The increased expression of miR-376b-3p attenuated starvation-induced autophagy in cell lines [ 24 ].…”

Section: Bioinformatic Analysis: Micrornas and Gpxsmentioning

confidence: 99%

MicroRNAs as Potential Regulators of Glutathione Peroxidases Expression and Their Role in Obesity and Related Pathologies

Matoušková

Hanousková

Skálová

2018

IJMS

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Glutathione peroxidases (GPxs) belong to the eight-member family of phylogenetically related enzymes with different cellular localization, but distinct antioxidant function. Several GPxs are important selenoproteins. Dysregulated GPx expression is connected with severe pathologies, including obesity and diabetes. We performed a comprehensive bioinformatic analysis using the programs miRDB, miRanda, TargetScan, and Diana in the search for hypothetical microRNAs targeting 3′untranslated regions (3´UTR) of GPxs. We cross-referenced the literature for possible intersections between our results and available reports on identified microRNAs, with a special focus on the microRNAs related to oxidative stress, obesity, and related pathologies. We identified many microRNAs with an association with oxidative stress and obesity as putative regulators of GPxs. In particular, miR-185-5p was predicted by a larger number of programs to target six GPxs and thus could play the role as their master regulator. This microRNA was altered by selenium deficiency and can play a role as a feedback control of selenoproteins’ expression. Through the bioinformatics analysis we revealed the potential connection of microRNAs, GPxs, obesity, and other redox imbalance related diseases.

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“…In this manner, miR-145 targets were identified in pancreatic cancer 50 and several putative miRNA targets were found in intestinal cell lines 51 . Furthermore, a crosstalk between proteome and non-coding RNAs was proposed by proteome and miRNome data during ongoing endothelial senescence 52 and during telomere shortening in cancer cells 53 . Possible targets for miR-23a, miR-24-2, and miR-27a were identified by mass spectrometry in pre B-lymphoblasts 54 .…”

Section: Discussionmentioning

confidence: 99%

Functional omics analyses reveal only minor effects of microRNAs on human somatic stem cell differentiation

Schira‐Heinen

Czapla

Hendricks

et al. 2020

Sci Rep

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The contribution of microRNA-mediated posttranscriptional regulation on the final proteome in differentiating cells remains elusive. Here, we evaluated the impact of microRNAs (miRNAs) on the proteome of human umbilical cord blood-derived unrestricted somatic stem cells (USSC) during retinoic acid (RA) differentiation by a systemic approach using next generation sequencing analysing mRNA and miRNA expression and quantitative mass spectrometry-based proteome analyses. Interestingly, regulation of mRNAs and their dedicated proteins highly correlated during RA-incubation. Additionally, RA-induced USSC demonstrated a clear separation from native USSC thereby shifting from a proliferating to a metabolic phenotype. Bioinformatic integration of up-and downregulated miRNAs and proteins initially implied a strong impact of the miRNome on the XXL-USSC proteome. However, quantitative proteome analysis of the miRNA contribution on the final proteome after ectopic overexpression of downregulated miR-27a-5p and miR-221-5p or inhibition of upregulated miR-34a-5p, respectively, followed by RA-induction revealed only minor proportions of differentially abundant proteins. In addition, only small overlaps of these regulated proteins with inversely abundant proteins in non-transfected RA-treated USSC were observed. Hence, mRNA transcription rather than miRNAmediated regulation is the driving force for protein regulation upon RA-incubation, strongly suggesting that miRNAs are fine-tuning regulators rather than active primary switches during RA-induction of USSC. MicroRNAs (miRNAs) are small non-coding RNAs which primarily bind to the 3′UTR of target mRNAs in a sequence-specific manner resulting in translational repression or destabilization and degradation of the targeted mRNA 1. In animals, primary miRNA transcripts are trimmed in a two-step process involving double strand-specific nucleases Drosha and Dicer. The mature single-stranded miRNA is then incorporated into the RNA-induced silencing complex (RISC) where functional binding to the mRNA target sequence takes place 1. As a most important feature, miRNA-mediated regulation is characterised by a bidirectional target gene redundancy. This allows a single miRNA to target the 3′ UTRs of hundreds of mRNAs in parallel 2. Vice versa, binding sites for several miRNAs can be found on a single 3′ UTR. In consequence of these properties, miRNAs primarily can act as network regulators being able to affect large numbers of regulatory targets in parallel 2,3 .

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Quantitative and integrated proteome and microRNA analysis of endothelial replicative senescence

Cited by 25 publications

References 77 publications

Menopause and adipose tissue: miR-19a-3p is sensitive to hormonal replacement

Menopause and adipose tissue: miR-19a-3p is sensitive to hormonal replacement

MicroRNAs as Potential Regulators of Glutathione Peroxidases Expression and Their Role in Obesity and Related Pathologies

Functional omics analyses reveal only minor effects of microRNAs on human somatic stem cell differentiation

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