miR-204-5p promotes the adipogenic differentiation of human adipose-derived mesenchymal stem cells by modulating DVL3 expression and suppressing Wnt/β-catenin signaling

He, Honghui; Chen, Ke; Wang, Fang; Zhao, Liling; Wan, Xinxing; Wang, Linghao; Zhang, Mo

doi:10.3892/ijmm.2015.2160

Cited by 63 publications

(50 citation statements)

References 31 publications

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“…Conversely, because basal miR-204 levels are higher in MAPC, the effects of miR-204 downregulation by transfecting MAPC with a miR-204 inhibitor were investigated. A number of publications have demonstrated that miR-204 plays a role in cell differentiation [43][44][45][46][47], and although effects may be cell-typedependent [44], a consistent positive effect of miR-204 on adipocyte differentiation had been described [43,47]. Consistent with these previous publications, knockdown of miR-204 in MAPC led to reduced adipocyte differentiation of MAPC as demonstrated by Oil-Red-O staining (Fig.…”

Section: Validation Of Mirna Function In Establishment Of Mapc Characsupporting

confidence: 83%

“…They have also been reported to be downregulated in aging cells, including MSCs [57]. As mentioned previously, miR-204 is known to regulate both osteoblast and adipocyte differentiation in vitro [43][44][45][46][47], but has also been associated with adipose tissue development in vivo [58,59]. Additionally the MAPC marker miR-155 has been shown to exert immune-modulatory functions in T cells, B cells, and dendritic cells [60][61][62][63][64].…”

Section: Discussionmentioning

confidence: 85%

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Using miRNA-mRNA Interaction Analysis to Link Biologically Relevant miRNAs to Stem Cell Identity Testing for Next-Generation Culturing Development

Crabbé

Gijbels²,

Visser³

et al. 2016

Stem Cells Translational Medicine

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Therapeutic benefit of stem cells has been demonstrated in multiple disease models and clinical trials. Robust quality assurance is imperative to make advancements in culturing procedures to enable large-scale cell manufacturing without hampering therapeutic potency. MicroRNAs (miRNAs or miRs) are shown to be master regulators of biological processes and are potentially ideal quality markers. We determined miRNA markers differentially expressed under nonclinical multipotent adult progenitor cell (MAPC) and mesenchymal stem cell (MSC) culturing conditions that regulate important stem cell features, such as proliferation and differentiation. These bone marrow-derived stem cell types were selected because they both exert therapeutic functions, but have different proliferative and regenerative capacities. To determine cell-specific marker miRNAs and assess their effects on stem cell qualities, a miRNA and mRNA profiling was performed on MAPCs and MSCs isolated from three shared donors. We applied an Ingenuity Pathway Analysis-based strategy that combined an integrated RNA profile analysis and a biological function analysis to determine the effects of miRNA-mRNA interactions on phenotype. This resulted in the identification of important miRNA markers linked to cell-cycle regulation and development, the most distinctive being MAPC marker miR-204-5p and MSC marker miR-335-5p, for which we provide in vitro validation of its function in differentiation and cell cycle regulation, respectively. Importantly, marker expression is maintained under xeno-free conditions and during bioreactor isolation and expansion of MAPC cultures. In conclusion, the identified biologically relevant miRNA markers can be used to monitor stem cell stability when implementing variations in culturing procedures. STEM CELLS TRANSLATIONAL MEDICINE 2016;5:709-722 SIGNIFICANCEHuman adult marrow stromal stem cells have shown great potential in addressing unmet health care needs. Quality assurance is imperative to make advancements in large-scale manufacturing procedures. MicroRNAs are master regulators of biological processes and potentially ideal quality markers. MicroRNA and mRNA profiling data of two human adult stem cell types were correlated to biological functions in silico. Doing this provided evidence that differentially expressed microRNAs are involved in regulating specific stem cell features. Furthermore, expression of a selected microRNA panel was maintained in next-generation culturing platforms, demonstrating the robustness of microRNA profiling in stem cell comparability testing.

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Section: Validation Of Mirna Function In Establishment Of Mapc Characsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 85%

Using miRNA-mRNA Interaction Analysis to Link Biologically Relevant miRNAs to Stem Cell Identity Testing for Next-Generation Culturing Development

Crabbé

Gijbels²,

Visser³

et al. 2016

Stem Cells Translational Medicine

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show abstract

“…Therefore, miR-204 is a “switch” molecule that controls the fate choice between osteogenesis and adipogenesis [9]. Consistently, miR-204 promotes the differentiation of human adipose-derived MSCs into mature adipoctyes [10]. Moreover, disheveled segment polarity protein 3 (DVL3), a key regulator of the Wnt/β-catenin signaling pathway, was identified as the target of miR-204.…”

Section: Physiological Functions Of Mir-204mentioning

confidence: 99%

“…In addition, overexpression of miR-204 was shown to induce the downregulation of β-catenin and the canonical Wnt target gene, CCND1, in mature adipoctyes, while its knockdown led to upregulation of CCND1. Therefore, miR-204 was proposed to regulate adipogenesis by controlling DVL3 expression and subsequently inhibiting the activation of the Wnt/β-catenin signaling pathway [10]. …”

Section: Physiological Functions Of Mir-204mentioning

confidence: 99%

The dual regulatory role of miR-204 in cancer

Pan

2016

Tumor Biol.

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MicroRNAs (miRNAs) are a group of endogenous, small (about 22 nucleotides) non-coding RNAs which negatively regulate gene expressions. As one of them, miR-204 originates from the sixth intron of the transient receptor potential melastatin 3 (TRPM3) gene. Therefore, expression of miR-204 is under the control of the TRPM3 promoter and regulated by genetic and epigenetic mechanisms. miR-204 has been found to play the important roles in development of eyes and adipogenesis. Its pathological functions have been observed in a few diseases including pulmonary arterial hypertension, diabetes, and various types of cancers. It is believed that miR-204 acts as a tumor-suppressor via promoting apoptosis, conferring the resistance of cancer cells to chemotherapy, and suppressing the self-renewal of cancer stem cells (CSCs) and the epithelial to mesenchymal transition (EMT). Expression of miR-204 is repressed by its targets XRN1 and TRKB in prostate cancer and endometrial carcinoma, respectively; therefore, they establish an oncogenic feedback loops that play an important role promoting development of cancer. In this review, we summarize our current knowledge regarding miR-204, including its expression, regulation and biological functions, especially focusing our discussion on its role in tumor development and tumor progression.

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“…Relatively little is known of the impact of post-transcriptional regulation of Dvl on Wnt signaling pathways (He et al, 2015;Huang et al, 2018). MicroRNAs (miRNAs) are small non-coding RNAs that regulate post-transcriptional gene expression by binding to the 3′ untranslated region (3′UTR) of target mRNAs to repress their translation and/or induce mRNA degradation (Bartel, 2009).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of microRNA suppression of Dishevelled results in Wnt pathway-associated developmental defects in sea urchin

et al. 2018

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MicroRNAs (miRNAs) are highly conserved, small non-coding RNAs that regulate gene expressions by binding to the 3′ untranslated region of target mRNAs thereby silencing translation. Some miRNAs are key regulators of the Wnt signaling pathways, which impact developmental processes. This study investigates miRNA regulation of different isoforms of Dishevelled (Dvl/Dsh), which encode a key component in the Wnt signaling pathway. The sea urchin Dvl mRNA isoforms have similar spatial distribution in early development, but one isoform is distinctively expressed in the larval ciliary band. We demonstrated that Dvl isoforms are directly suppressed by miRNAs. By blocking miRNA suppression of Dvl isoforms, we observed dosedependent defects in spicule length, patterning of the primary mesenchyme cells, gut morphology, and cilia. These defects likely result from increased Dvl protein levels, leading to perturbation of Wnt-dependent signaling pathways and additional Dvl-mediated processes. We further demonstrated that overexpression of Dvl isoforms recapitulated some of the Dvl miRNATP-induced phenotypes. Overall, our results indicate that miRNA suppression of Dvl isoforms plays an important role in ensuring proper development and function of primary mesenchyme cells and cilia.

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miR-204-5p promotes the adipogenic differentiation of human adipose-derived mesenchymal stem cells by modulating DVL3 expression and suppressing Wnt/β-catenin signaling

Cited by 63 publications

References 31 publications

Using miRNA-mRNA Interaction Analysis to Link Biologically Relevant miRNAs to Stem Cell Identity Testing for Next-Generation Culturing Development

Using miRNA-mRNA Interaction Analysis to Link Biologically Relevant miRNAs to Stem Cell Identity Testing for Next-Generation Culturing Development

The dual regulatory role of miR-204 in cancer

Inhibition of microRNA suppression of Dishevelled results in Wnt pathway-associated developmental defects in sea urchin

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