LncRNA Gm15290 sponges miR-27b to promote PPARγ-induced fat deposition and contribute to body weight gain in mice

Liu, Weihua; Ma, Chunli; Yang, Bin; Chen, Yin; Zhang, Beining; Xiao, Yanfeng

doi:10.1016/j.bbrc.2017.09.114

Cited by 57 publications

(40 citation statements)

References 21 publications

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“…In recent years, an increasing number of reports have showed that lncRNAs can act as ceRNAs by competitively binding to microRNAs (miRNAs), inhibiting miRNA activity and regulating mRNA expression. The lncRNA Gm15290 sponges miR-27b to promote PPARγmediated adipogenesis in vitro and to increase fat deposition and body weight in high-fat diet-(HFD-) fed mice [26]. The lncRNA H19 acts as a ceRNA of miR-30a to enhance the expression of the downstream C8orf4, modulating adipogenic differentiation in human adipose tissuederived mesenchymal stem cells [27].…”

Section: Introductionmentioning

confidence: 99%

The Construction and Analysis of the Aberrant lncRNA-miRNA-mRNA Network in Adipose Tissue from Type 2 Diabetes Individuals with Obesity

Ding

Wang

et al. 2020

Journal of Diabetes Research

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Background. The prevalence of obesity and type 2 diabetes mellitus (T2DM) has become the most serious global public health issue. In recent years, there has been increasing attention to the role of long noncoding RNAs (lncRNAs) in the occurrence and development of obesity and T2DM. The aim of this work was to find new lncRNAs as potential predictive biomarkers or therapeutic targets for obesity and T2DM. Methods. In this study, we identified significant differentially expressed mRNAs (DEmRNAs) and differentially expressed lncRNAs (DElncRNAs) between adipose tissue of individuals with obesity and T2DM and normal adipose tissue (absolute log 2 FC ≥ 1 and FDR < 0:05). Then, the lncRNA-miRNA interactions predicted by miRcode were further screened with a threshold of MIC > 0:2. Simultaneously, the mRNA-miRNA interactions were explored by miRWalk 2.0. Finally, a ceRNA network consisting of lncRNAs, miRNAs, and mRNAs was established by integrating lncRNA-miRNA interactions and mRNA-miRNA interactions. Results. Upon comparing adipose tissue from individuals with obesity and T2DM and normal adipose tissues, 364 significant DEmRNAs, including 140 upregulated and 224 downregulated mRNAs, were identified in GSE104674; in addition, 231 significant DEmRNAs, including 146 upregulated and 85 downregulated mRNAs, were identified in GSE133099. GO and KEGG analyses have shown that downregulated DEmRNAs in GSE104674 and GSE133099 were associated with obesity-and T2DM-related biological pathways, such as lipid metabolism, AMPK signaling, and insulin resistance. Furthermore, 28 significant DElncRNAs, including 14 upregulated and 14 downregulated lncRNAs, were found. Based on the predicted lncRNA-miRNA and mRNA-miRNA relationships, we constructed a competitive endogenous RNA (ceRNA) network, including five lncRNAs, ten miRNAs, and 15 mRNAs. KEGG-GSEA analysis revealed that four lncRNAs (FLG-AS1, SNAI3-AS1, AC008147.0, and LINC02015) in the ceRNA network were related to the biological pathways of metabolic diseases. Conclusions. Through ceRNA network analysis, our study identified four new lncRNAs that may be used as potential biomarkers and therapeutic targets of obesity and T2DM, thus laying a foundation for future clinical studies.

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Section: Introductionmentioning

confidence: 99%

The Construction and Analysis of the Aberrant lncRNA-miRNA-mRNA Network in Adipose Tissue from Type 2 Diabetes Individuals with Obesity

Ding

Wang

et al. 2020

Journal of Diabetes Research

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“…However, many of these are also required at the differentiation stage. Liu et al, 2017;Nuermaimaiti et al, 2018;Xiao et al, 2015;Xiong et al, 2018). In contrast, our knockdown studies indicate that LINC00473 is not required for differentiation, but rather for more specific aspects of thermogenic adipocyte function, as discussed below.…”

Section: Discussionmentioning

confidence: 99%

A long-non-coding RNA, LINC00473, confers the human adipose tissue thermogenic phenotype through enhanced cAMP responsiveness

Tran

Nandrup-Bus

DeSouza

et al. 2018

Preprint

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SummarySpecialized adipocytes localized in distinct depots mediate the many physiological functions of adipose tissue. In humans, paucity of thermogenic adipocytes correlates with high metabolic disease risk, raising much interest in the mechanisms by which these cells arise. Here we report molecular signatures associated with adipocyte development in different human depots and identify a long non-coding RNA, LINC00473, as the transcript most closely associated with enrichment of thermogenic adipocytes.LINC00473 expression is low in subjects with obesity or type-2 diabetes and is highly correlated with cAMP signaling and mitochondrial oxidative phosphorylation pathways. LINC00473 is localized in the nucleus and the cytoplasm, and its knockdown impairs induction of UCP1 and mitochondrial respiration.These results reveal that depot-enriched genes that modulate responsiveness to external stimuli, specifically LINC00473, are important determinants of the adipose tissue thermogenic phenotype, and potential targets for metabolic disease therapy.

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“…Studies have demonstrated that lncRNAs can interact with protein-coding genes through direct competition for miRNA binding [20]. For example, Liu et al [21] found that lncRNA Gm15290 sponges miR-27b to promote PPARγ-mediated adipogenesis in vitro and increase fat deposition and body weight in high fat dietfed mice.…”

Section: Introductionmentioning

confidence: 99%

Relationship among porcine lncRNA TCONS_00010987, miR-323, and leptin receptor based on dual luciferase reporter gene assays and expression patterns

Ding

Wang

et al. 2020

Asian-Australas J Anim Sci

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Considering the physiological and clinical importance of leptin receptor (LEPR) in regulating obesity and the fact that porcine LEPR expression is not known to be controlled by lncRNAs and miRNAs, we aim to characterize this gene as a potential target of SSC-miR-323 and the lncRNA TCONS_00010987. Methods: Bioinformatics analyses revealed that lncRNA TCONS_00010987 and LEPR have SSC-miR-323-binding sites and that LEPR might be a target of lncRNA TCONS_00010987 based on cis prediction. Wild-type and mutant TCONS_00010987-target sequence fragments and wild-type and mutant LEPR 3′-UTR fragments were generated and cloned into pmiR-RB-REPORT TM-Control vectors to construct respective recombinant plasmids. HEK293T cells were co-transfected with the SSC-miR-323 mimics or a negative control with constructs harboring the corresponding binding sites and relative luciferase activities were determined. Tissue expression patterns of lncRNA TCONS_00010987, SSC-miR-323, and LEPR in Anqing six-end-white (AQ, the obese breed) and Large White (LW, the lean breed) pigs were detected by real-time quantitative polymerase chain reaction; backfat expression of LEPR protein was detected by western blotting. Results: Target gene fragments were successfully cloned, and the four recombinant vectors were constructed. Compared to the negative control, SSC-miR-323 mimics significantly inhibited luciferase activity from the wild-type TCONS_00010987-target sequence and wildtype LEPR-3′-UTR (p<0.01 for both) but not from the mutant TCONS_00010987-target sequence and mutant LEPR-3′-UTR (p>0.05 for both). Backfat expression levels of TCONS_ 00010987 and LEPR in AQ pigs were significantly higher than those in LW pigs (p<0.01), whereas levels of SSC-miR-323 in AQ pigs were significantly lower than those in LW pigs (p<0.05). LEPR protein levels in the backfat tissues of AQ pigs were markedly higher than those in LW pigs (p<0.01). Conclusion: LEPR is a potential target of SSC-miR-323, and TCONS_00010987 might act as a sponge for SSC-miR-323 to regulate LEPR expression.

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LncRNA Gm15290 sponges miR-27b to promote PPARγ-induced fat deposition and contribute to body weight gain in mice

Cited by 57 publications

References 21 publications

The Construction and Analysis of the Aberrant lncRNA-miRNA-mRNA Network in Adipose Tissue from Type 2 Diabetes Individuals with Obesity

The Construction and Analysis of the Aberrant lncRNA-miRNA-mRNA Network in Adipose Tissue from Type 2 Diabetes Individuals with Obesity

A long-non-coding RNA, LINC00473, confers the human adipose tissue thermogenic phenotype through enhanced cAMP responsiveness

Relationship among porcine lncRNA TCONS_00010987, miR-323, and leptin receptor based on dual luciferase reporter gene assays and expression patterns

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