MiR-183 promotes preadipocyte differentiation by suppressing Smad4 in goats

Zhao, Wei; Yang, Hailong; Li, Juntao; Chen, Yuan; Cao, Jiaxue; Zhong, Tao; Wang, Linjie; Guo, Jiazhong; Li, Li; Zhang, Hongping

doi:10.1016/j.gene.2018.05.022

Cited by 17 publications

(13 citation statements)

References 37 publications

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“…Moreover, the SMAD4 and TGF-β signaling pathways play important roles in miRNA regulation of cell proliferation [41,42]. Notably, miR-183 promotes preadipocyte adipogenesis by suppressing SMAD4 expression in goats [43], and myostatin/SMAD4 signaling inhibits 3T3-L1 cell differentiation [44]. These ndings demonstrate that the effects of SMAD4 on adipocyte differentiation vary in different cell types.…”

Section: Discussionmentioning

confidence: 86%

MiR-146a-5p targeting SMAD4 and TRAF6 inhibits adipogenensis through TGF-β and AKT/mTORC1 signal pathways in porcine intramuscular preadipocytes

Zhang

Cai

Tang

et al. 2020

Preprint

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Background: Intramuscular fat (IMF) content is a vital parameter for assessing pork quality. Increasing evidence has shown that microRNAs (miRNAs) play an important role in regulating porcine IMF deposition. Here, a novel miRNA implicated in porcine IMF adipogenesis was found, and its effect and regulatory mechanism were further explored with respect to intramuscular preadipocyte proliferation and differentiation.Results: By porcine adipose tissue miRNA sequencing analysis, we found that miR-146a-5p is a potential regulator of porcine IMF adipogenesis. Further studies showed that miR-146a-5p mimics inhibited porcine intramuscular preadipocyte proliferation and differentiation, while the miR-146a-5p inhibitor promoted cell proliferation and adipogenic differentiation. Mechanistically, miR-146a-5p suppressed cell proliferation by directly targeting SMAD family member 4 (SMAD4) to attenuate TGF-β signaling. Moreover, miR-146a-5p inhibited the differentiation of intramuscular preadipocytes by targeting TNF receptor-associated factor 6 (TRAF6) to weaken the AKT/mTORC1 signaling downstream of the TRAF6 pathway.Conclusions: MiR-146a-5p targets SMAD4 and TRAF6 to inhibit porcine intramuscular adipogenesis by attenuating TGF-β and AKT/mTORC1 signaling, respectively. These findings provide a novel miRNA biomarker for regulating intramuscular adipogenesis to promote pork quality.

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Section: Discussionmentioning

confidence: 86%

MiR-146a-5p targeting SMAD4 and TRAF6 inhibits adipogenensis through TGF-β and AKT/mTORC1 signal pathways in porcine intramuscular preadipocytes

Zhang

Cai

Tang

et al. 2020

Preprint

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“…miRNAs have also been shown to be involved in cell differentiation (Zhang et al, 2017). In goats, miR-183 promotes preadipocyte differentiation by suppressing the expression of Smad4 (Zhao et al, 2018) and miR-21a-5p induces preadipocyte differentiation by targeting Mitogen-activated protein kinase 2/kinase 3 (MAPK2K3) through MKK3/p38/MAPK signaling pathway in mice (Xie et al, 2016). MiR-33b downregulates the differentiation of porcine preadipocytes (Taniguchi et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

MiR-9-5p promotes rabbit preadipocyte differentiation by suppressing leptin gene expression

Luo

Lai

et al. 2020

Preprint

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Background: MicroRNAs (miRNAs) are a class of small non-coding RNAs, which participate in the regulation of cell differentiation. Previous studies have demonstrated that miR-9-5p plays a key role in cancer cell development, but the mechanisms by which miR-9-5p regulates adipogenesis remain poorly understood. The present study intended to investigate its significance in producing rabbits with high-quality meat by observing the regulatory effect of miR-9-5p in preadipocytes and finding the related targets. Methods: In this study, a dual-luciferase reporter assay was employed to validate the targeting relationship between miR-9-5p and leptin gene. We also utilized quantitative reverse transcription PCR (qRT-PCR), western blot, oil red-O staining assay, and determination of triglyceride content to analyze the regulation of miR-9-5p and leptin gene during adipocyte differentiation. Results: The analysis demonstrated that during preadipocyte differentiation, miR-9-5p was up-regulated and the fat formation related biomarkers, i.e., fatty acid-binding protein 4 (FABP4), CCAAT-enhancer binding protein α (C/EBPα), and peroxisome proliferator activated receptor γ (PPARγ) were also up-regulated. Meanwhile, the oil red-O staining assay revealed that the accumulation of lipid droplets increased. We also explored the expression pattern and role of miR-9-5p in adipogenesis using white pre-adipocytes. The results showed that miR-9-5p was up-regulated during preadipocyte differentiation, and overexpression of miR-9-5p enhanced lipid accumulation. Furthermore, we found that the overexpression of miR-9-5p significantly up- regulated the expression of marker genes, PPARγ, C/EBPα and FABP4, and increased the protein levels of PPARγ and triglyceride content. The results suggest that miR-9-5p might be involved in the regulation of rabbit preadipocyte differentiation. We predicted that leptin is the target gene of miR-9-5p, by using bioinformatics tools and the conclusion was validated by a luciferase reporter assay. Finally, we verified that the knock-down of leptin by si-leptin promoted preadipocyte differentiation in rabbits. Conclusion: The results of the present study indicate that miR-9-5p regulates white preadipocyte differentiation in rabbits by targeting the leptin gene.

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“…13 miRNAs are involved in a number of pathological and physiological processes; for example, miRNAs influence cell proliferation, cell cycle progression, and apoptosis. Zhao et al 16 further found that miR-183 upregulates goat preadipocyte differentiation by targeting Smad4, 16 and Shuai et al 17 reported that miR-204 negatively regulates cell development and motility by repressing CXCL8 in colorectal cancer (CRC) cells. For instance, Lee et al 14 showed that miR-130 suppresses adipogenesis by attenuating PPARγ, and Zhang et al 15 found that miR-143a-3p accelerates preadipocyte differentiation and suppresses preadipocyte proliferation by attenuating mitogen-activated protein kinase 7.…”

Section: Introductionmentioning

confidence: 99%

“…For instance, Lee et al 14 showed that miR-130 suppresses adipogenesis by attenuating PPARγ, and Zhang et al 15 found that miR-143a-3p accelerates preadipocyte differentiation and suppresses preadipocyte proliferation by attenuating mitogen-activated protein kinase 7. Zhao et al 16 further found that miR-183 upregulates goat preadipocyte differentiation by targeting Smad4, 16 and Shuai et al 17 reported that miR-204 negatively regulates cell development and motility by repressing CXCL8 in colorectal cancer (CRC) cells. 17 Huang et al 18 found that miR-204 suppresses osteogenesis and facilitates adipogenesis by targeting Runx2 in mesenchymal progenitor cells and bone marrow stem cells.…”

mentioning

confidence: 99%

ssc‐miR‐204 regulates porcine preadipocyte differentiation and apoptosis by targeting TGFBR1 and TGFBR2

Zhang

Wang

et al. 2019

J of Cellular Biochemistry

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MicroRNAs (miRNAs) take part in a variety of biological processes by regulating target genes. Transforming growth factor β receptor 1 (TGFBR1) and TGFBR2 are crucial members of the TGF‐β family and are serine/threonine kinase receptors. The aim of this study was to explore the functions of ssc‐miR‐204 in porcine preadipocyte differentiation and apoptosis with regard to the TGFβ/Smad pathway. We identified miRNAs predicted to target TGFBR1 and TGFBR2 using a database and selected ssc‐miR‐204 as a candidate miRNA. ssc‐miR‐204 overexpression dramatically reduced the levels of TGFBR1 and TGFBR2. However, after transfection with ssc‐miR‐204 inhibitor, TGFBR1 and TGFBR2 levels were dramatically increased. ssc‐miR‐204 overexpression dramatically promoted porcine preadipocyte differentiation and apoptosis. After transfection with ssc‐miR‐204 inhibitor, porcine preadipocyte differentiation and apoptosis were dramatically inhibited. After transfection with ssc‐miR‐204 mimics, Smad2, Smad3, Smad4, p‐Smad2, and p‐Smad3 protein levels significantly decreased, and adipogenesis was regulated by inhibiting the TGF‐β/Smad3 signaling pathway. Taken together, these results verified that ssc‐miR‐204 regulates porcine preadipocyte differentiation and apoptosis by targeting TGFBR1 and TGFBR2.

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MiR-183 promotes preadipocyte differentiation by suppressing Smad4 in goats

Cited by 17 publications

References 37 publications

MiR-146a-5p targeting SMAD4 and TRAF6 inhibits adipogenensis through TGF-β and AKT/mTORC1 signal pathways in porcine intramuscular preadipocytes

MiR-146a-5p targeting SMAD4 and TRAF6 inhibits adipogenensis through TGF-β and AKT/mTORC1 signal pathways in porcine intramuscular preadipocytes

MiR-9-5p promotes rabbit preadipocyte differentiation by suppressing leptin gene expression

ssc‐miR‐204 regulates porcine preadipocyte differentiation and apoptosis by targeting TGFBR1 and TGFBR2

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