MicroRNA-425 controls lipogenesis and lipolysis in adipocytes

Qi, Renli; Wang, Jing; Wang, Qi; Qiu, Xiaoyu; Yang, Feiyun; Liu, Zuohua; Huang, Jinxiu

doi:10.1016/j.bbalip.2019.02.007

Cited by 34 publications

(28 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Novel miRNAs were identified through high‐throughput sequencing and microarray analysis in animals (Ambros, 2004). Previous literature has confirmed the role of miR‐709 (H. Chen et al, 2014), miR‐448 (Kinoshita et al, 2010), miR‐185 (Ning et al, 2017), miR‐130 (E. K. Lee et al, 2011), miR‐27a/b (Kang et al, 2013; Lin, Gao, Alarcon, Ye, & Yun, 2009), miR‐23a (Huang et al, 2016; Shen et al, 2016), miR‐21a (Xie, Song, & Li, 2016), and let‐7 (Sun, Fu, Bookout, Kliewer, & Mangelsdorf, 2009) in the reduction of lipogenesis through negative regulation of adipocyte differentiation, whereas miR‐21 (An et al, 2016; Kang et al, 2013), miR‐26b (G. Li et al, 2017), miR‐143 (Yi et al, 2011), miR‐148 (Shi et al, 2015), miR‐183 (C. Chen, Xiang, Peng, Peng, & Jiang, 2014), and miR‐425 (Qi et al, 2019) positively regulated adipocyte differentiation. In the present study, the function of bta‐miR‐149‐5p was investigated; at first, the spatiotemporal expression level of bta‐miR‐149‐5p in different bovine tissues showed greater expression level in fat tissue after rumen and lungs tissues.…”

Section: Discussionmentioning

confidence: 99%

“…Novel miRNAs were identified through high-throughput sequencing and microarray analysis in animals (Ambros, 2004). Previous literature has confirmed the role of miR-709 (H. , miR-448 (Kinoshita et al, 2010), miR-185 ), miR-130 (E. K. Lee et al, 2011, miR-27a/b Lin, Gao, Alarcon, Ye, & Yun, 2009), miR-23a (Huang et al, 2016;Shen et al, 2016), miR-21a (Xie, Song, & Li, 2016), and let-7 (Sun, Fu, Bookout, Kliewer, & Mangelsdorf, 2009) in the reduction of lipogenesis through negative regulation of adipocyte differentiation, whereas miR-21 , miR-26b (G. Li et al, 2017), miR-143 (Yi et al, 2011), miR-148 , miR-183 (C. Chen, Xiang, Peng, Peng, & Jiang, 2014), and miR-425 (Qi et al, 2019) In addition, bioinformatics analysis was used to predict and dualluciferase reporter assay, qRT-PCR, and western blot analysis were used to validate CRTC1 and CRTC2 as the direct target genes of bta-miR-149-5p. Bioinformatics study further revealed the highest enrichment scores of bta-miR-149-5p for the cAMP and Calcium signaling pathways.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Bta‐miR‐149‐5p inhibits proliferation and differentiation of bovine adipocytes through targeting CRTCs at both transcriptional and posttranscriptional levels

Khan

Raza

Junjvlieke

et al. 2020

Journal Cellular Physiology

View full text Add to dashboard Cite

MicroRNAs are small, single stranded, and noncoding RNAs that have been proven to be potent regulators of adipogenesis. However, the role of bta‐miR‐149‐5p in regulating bovine adipogenesis is still unclear. Expression profiling in different stages of adipogenesis revealed that bta‐miR‐149‐5p was enriched in the proliferation stage, and also on Day 9 of differentiation in bovine adipocytes. Our gain of function study showed that bta‐miR‐149‐5p can negatively regulate both bovine adipocyte proliferation and differentiation. Overexpression of bta‐miR‐149‐5p suppressed the expression of proliferation marker genes at both the messenger RNA (mRNA) and protein levels, markedly decreased the percentage of S‐phase cells, decreased the number of EdU‐stained cells, and substantially reduced adipocyte proliferation vitality in the cell count assay. Collectively, these findings elucidated that bta‐miR‐149‐5p inhibits adipocyte proliferation. Furthermore, overexpression of bta‐miR‐149‐5p also suppressed the expression of adipogenic genes at both the mRNA and protein levels, inhibited lipid accumulation, and reduced the secretion of adiponectin in bovine adipocytes. Furthermore, a luciferase activity assay explored how bta‐miR‐149‐5p targeted CRTCs (CRTC1 and CRTC2) directly. This targeting was further validated by the mRNA and protein level expression of CRTC1 and CRTC2, which were down regulated by bta‐miR‐149‐5p overexpression. Moreover, bta‐miR‐149‐5p indirectly targeted CRTC1 and CRTC2 through regulating their key transcription factors. Overexpression of bta‐miR‐149‐5p suppressed the expression of SMAD3, while enriched the expression of NRF1, which are the key transcription factors and proven regulators of CRTC1. Overexpression of bta‐miR‐149‐5p also repressed the expression of C/EBPγ, XBP1, INSM1, and ZNF263, which are the key regulators of CRTCs, at both the mRNA and protein levels. These findings suggest that bta‐miR‐149‐5p is a negative regulator of CRTC1 and CRTC2 both at transcriptional and posttranscriptional level. Taken together, these findings suggest that bta‐miR‐149‐5p can regulate adipogenesis, which implies that bta‐miR‐149‐5p could be a target for increasing intramuscular fat in beef cattle.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Bta‐miR‐149‐5p inhibits proliferation and differentiation of bovine adipocytes through targeting CRTCs at both transcriptional and posttranscriptional levels

Khan

Raza

Junjvlieke

et al. 2020

Journal Cellular Physiology

View full text Add to dashboard Cite

show abstract

“…The miR-425 family (including miR-425-3p and miR-425-5p) participates in biological processes occurring in the gastrointestinal tract, among other tissues, and its abnormal expression is associated with the progression of several diseases (Lu et al, 2019). Interestingly, the increase in miR-425 levels is useful for fat production in muscle cells and adipocytes (Qi et al, 2019). According to the results shown here, miR-425-5p appears to be important in the regulation of lipid metabolism, ketogenesis, and intestinal differentiation in enterocytes.…”

Section: Validation Confirms Five Selected Mirnasmentioning

confidence: 99%

Intestinal Lipid Metabolism Genes Regulated by miRNAs

Ruiz-Roso¹,

Gil-Zamorano²,

Hazas³

et al. 2020

Front. Genet.

View full text Add to dashboard Cite

MicroRNAs (miRNAs) crucial roles in translation repression and post-transcriptional adjustments contribute to regulate intestinal lipid metabolism. Even though their actions in different metabolic tissues have been elucidated, their intestinal activity is yet unclear. We aimed to investigate intestinal miRNA-regulated lipid metabolism-related genes, by creating an intestinal-specific Dicer1 knockout (Int-Dicer1 KO) mouse model, with a depletion of microRNAs in enterocytes. The levels of 83 cholesterol and lipoprotein metabolism-related genes were assessed in the intestinal mucosa of Int-Dicer1 KO and Wild Type C57BL/6 (WT) littermates mice at baseline and 2 h after an oral lipid challenge. Among the 18 genes selected for further validation, Hmgcs2, Acat1 and Olr1 were found to be strong candidates to be modulated by miRNAs in enterocytes and intestinal organoids. Moreover, we report that intestinal miRNAs contribute to the regulation of intestinal epithelial differentiation. Twenty-nine common miRNAs found in the intestines were analyzed for their potential to target any of the three candidate genes found and validated by miRNA-transfection assays in Caco-2 cells. MiR-31-5p, miR-99b-5p, miR-200a-5p, miR-200b-5p and miR-425-5p are major regulators of these lipid metabolism-related genes. Our data provide new evidence on the potential of intestinal miRNAs as therapeutic targets in lipid metabolism-associated pathologies.

show abstract

“…OxS is a vital phenomenon occurring in plethora of metabolic disorders including type 2 diabetes (T2DM), obesity and cancer [9,10]. Numerous studies have recently reported a link between OxS and miRNAs, the pivotal regulators of different aspects of glucose homeostasis, such as peripheral insulin signaling, β-cells function, lipogenesis, and chronic inflammation [6,[11][12][13][14][15]. For instance, miRNAs directly and indirectly influence he expression level or activity of antioxidative defense genes or ones generating ROS, thereby having an impact on redox balance [16][17][18][19][20][21][22][23].…”

Section: Introductionmentioning

confidence: 99%

The Role of microRNAs in Metabolic Syndrome-Related Oxidative Stress

Włodarski

Strycharz

Wróblewski

et al. 2020

IJMS

View full text Add to dashboard Cite

Oxidative stress (OxS) is the cause and the consequence of metabolic syndrome (MetS), the incidence and economic burden of which is increasing each year. OxS triggers the dysregulation of signaling pathways associated with metabolism and epigenetics, including microRNAs, which are biomarkers of metabolic disorders. In this review, we aimed to summarize the current knowledge regarding the interplay between microRNAs and OxS in MetS and its components. We searched PubMed and Google Scholar to summarize the most relevant studies. Collected data suggested that different sources of OxS (e.g., hyperglycemia, insulin resistance (IR), hyperlipidemia, obesity, proinflammatory cytokines) change the expression of numerous microRNAs in organs involved in the regulation of glucose and lipid metabolism and endothelium. Dysregulated microRNAs either directly or indirectly affect the expression and/or activity of molecules of antioxidative signaling pathways (SIRT1, FOXOs, Keap1/Nrf2) along with effector enzymes (e.g., GPx-1, SOD1/2, HO-1), ROS producers (e.g., NOX4/5), as well as genes of numerous signaling pathways connected with inflammation, insulin sensitivity, and lipid metabolism, thus promoting the progression of metabolic imbalance. MicroRNAs appear to be important epigenetic modifiers in managing the delicate redox balance, mediating either pro- or antioxidant biological impacts. Summarizing, microRNAs may be promising therapeutic targets in ameliorating the repercussions of OxS in MetS.

show abstract

MicroRNA-425 controls lipogenesis and lipolysis in adipocytes

Cited by 34 publications

References 53 publications

Bta‐miR‐149‐5p inhibits proliferation and differentiation of bovine adipocytes through targeting CRTCs at both transcriptional and posttranscriptional levels

Bta‐miR‐149‐5p inhibits proliferation and differentiation of bovine adipocytes through targeting CRTCs at both transcriptional and posttranscriptional levels

Intestinal Lipid Metabolism Genes Regulated by miRNAs

The Role of microRNAs in Metabolic Syndrome-Related Oxidative Stress

Contact Info

Product

Resources

About