Characterization of the promoter region of the bovine long-chain acyl-CoA synthetase 1 gene: Roles of E2F1, Sp1, KLF15 and E2F4

Zhao, Zhidong; Liu, Zan; Li, An-Ning; Chen, Gong; Li, Shijun; Zhang, Yaran; Wang, Xiaoyu; Zhang, Yingying

doi:10.1038/srep19661

Cited by 34 publications

(30 citation statements)

References 53 publications

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“…A number of target genes for KLF15 including S LC2A4 have been identified in rodent adipocyte [32, 38–41]. These genes, however, were not detected as targeted by KLF15 in our experiments in human cells.…”

Section: Discussioncontrasting

confidence: 49%

Global transcriptome profiling identifies KLF15 and SLC25A10 as modifiers of adipocytes insulin sensitivity in obese women

et al. 2017

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Although the mechanisms linking obesity to insulin resistance (IR) and type 2 diabetes (T2D) are not entirely understood, it is likely that alterations of adipose tissue function are involved. The aim of this study was to identify new genes controlling insulin sensitivity in adipocytes from obese women with either insulin resistant (OIR) or sensitive (OIS) adipocytes. Insulin sensitivity was first determined by measuring lipogenesis in isolated adipocytes from abdominal subcutaneous white adipose tissue (WAT) in a large observational study. Lipogenesis was measured under conditions where glucose transport was the rate limiting step and reflects in vivo insulin sensitivity. We then performed microarray-based transcriptome profiling on subcutaneous WAT specimen from a subgroup of 9 lean, 21 OIS and 18 obese OIR women. We could identify 432 genes that were differentially expressed between the OIR and OIS group (FDR ≤5%). These genes are enriched in pathways related to glucose and amino acid metabolism, cellular respiration, and insulin signaling, and include genes such as SLC2A4, AKT2, as well as genes coding for enzymes in the mitochondria respiratory chain. Two IR-associated genes, KLF15 encoding a transcription factor and SLC25A10 encoding a dicarboxylate carrier, were selected for functional evaluation in adipocytes differentiated in vitro. Knockdown of KLF15 and SLC25A10 using siRNA inhibited insulin-stimulated lipogenesis in adipocytes. Transcriptome profiling of siRNA-treated cells suggested that KLF15 might control insulin sensitivity by influencing expression of PPARG, PXMP2, AQP7, LPL and genes in the mitochondrial respiratory chain. Knockdown of SLC25A10 had only modest impact on the transcriptome, suggesting that it might directly influence insulin sensitivity in adipocytes independently of transcription due to its important role in fatty acid synthesis. In summary, this study identifies novel genes associated with insulin sensitivity in adipocytes in women independently of obesity. KFL15 and SLC25A10 are inhibitors of insulin-stimulated lipogenesis under conditions when glucose transport is the rate limiting step.

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Section: Discussioncontrasting

confidence: 49%

Global transcriptome profiling identifies KLF15 and SLC25A10 as modifiers of adipocytes insulin sensitivity in obese women

et al. 2017

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“…[26][27][28] It can bind to specific sites on the promoter of vascular endothelial growth factor (VEGF) or VEGF receptor, which further promotes the progress of tumors. 29 SP1-regulated tumor-related genes are involved in a variety of cell functions, including cell cycle (Cyclin D1, TGF-α, E2F1), 30,31 apoptosis (Bax, Bcl2), 32,33 tumor metastasis (TGF-β, MMP2) 34 and angiogenesis (VEGF). 35 According to our results, Syncytin 1 may be one of the targets of SP1 in regulating the function of cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Knockdown of SP1/Syncytin1 axis inhibits the proliferation and metastasis through the AKT and ERK1/2 signaling pathways in non‐small cell lung cancer

Xia

et al. 2019

Cancer Medicine

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Syncytin 1 is considered as an oncogene in various malignant tumors, but its effect on non‐small cell lung cancer (NSCLC) has not been reported. We investigated the specific role of Syncytin 1 on NSCLC through the transfection of Syncytin 1 knockdown or overexpression plamids in A549 cells. Our results proved that knockdown of Syncytin 1 inhibited the proliferation, and blocked the cell cycle on G1 phase by inhibiting the expression of Nusap1, Cyclin D1, CDK6, and CDK4. Cell cycle arrest also leaded to increased apoptosis in Syncytin 1 knockdown cells. Suppression of Syncytin 1 inhibited the migration and invasion, as well as the expressions of epithelial‐mesenchymal transition (EMT) makers, N‐cadherin, β‐catenin, and Vimentin, indicating that Syncytin 1 knockdown inhibited the metastasis via reversing the EMT process in A549 cells. The phosphorylation levels of Akt, mTOR, and Erk1/2 were all decreased in Syncytin 1 knockdown cells, suggesting the signaling pathways by which Syncytin 1 operated as an oncogene in NSCLC. Moreover, the underexpression of transcription factor SP1 downregulated the Syncytin 1 expression in A549 cells. The rescue experiment of Syncytin 1 in SP1 knockdown cells further proved that Syncytin 1 could block the inhibition of cell growth induced by SP1 knockdown. In conclusion, knockdown of SP1/Syncytin1 axis inhibited the progression of NSCLC by the reversion of tumor epithelial‐mesenchymal transition process and suppression of Akt and Erk signaling pathways, suggesting that they are potential targets for targeted therapy of NSCLC.

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“…Polymorphism in the promoter region is of great importance because the promoter region contains cis-acting elements that bind with transcription factors and regulate the respective gene [22][23][24][25]. For example, single nucleotide polymorphisms in the STAT3 [23], SIRT3 [26], KLF3 [27] SIX1 [24] and SIX4 [28] genes promoter regions impacted body measurement and meat quality traits in the Qinchuan cattle breed.…”

Section: Introductionmentioning

confidence: 99%

Genetic variants in the TORC2 gene promoter and their association with body measurement and carcass quality traits in Qinchuan cattle

et al. 2020

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The TORC2 gene is responsible for nutrient metabolism, gluconeogenesis, myogenesis and adipogenesis through the PI3K-Akt, AMPK, glucagon and insulin resistance signaling pathways. Sequencing of PCR amplicons explored three novel SNPs at loci g.16534694G>A, g.16535011C>T, and g.16535044A>T in the promoter region of the TORC2 gene in the Qinchuan breed of cattle. Allelic and genotypic frequencies of these SNPs deviated from Hardy-Weinberg equilibrium (HWE) (P < 0.05). SNP1 genotype GG, SNP2 genotype CT and SNP3 genotype AT showed significantly (P <0.05) larger body measurement and improved carcass quality traits. Haplotype H1 (GCA) showed significantly (p<0.01) higher transcriptional activity (51.44%) followed by H4 (ATT) (34.13%) in bovine preadipocytes. The diplotypes HI-H3 (GG-CC-AT), H1-H2 (GG-CT-AT) and H3-H4 (GA-CT-TT) showed significant (P<0.01) associations with body measurement and improved carcass quality traits. Analysis of the relative mRNA expression level of the TORC2 gene in different tissues within two different age groups revealed a significant increase (P<0.01) in liver, small intestine, muscle and fat tissues with growth from calf stage to adult stage. We can conclude that variants mapped within TORC2 can be used in marker-assisted selection for carcass quality and body measurement traits in breed improvement programs of Qinchuan cattle.

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Characterization of the promoter region of the bovine long-chain acyl-CoA synthetase 1 gene: Roles of E2F1, Sp1, KLF15 and E2F4

Cited by 34 publications

References 53 publications

Global transcriptome profiling identifies KLF15 and SLC25A10 as modifiers of adipocytes insulin sensitivity in obese women

Global transcriptome profiling identifies KLF15 and SLC25A10 as modifiers of adipocytes insulin sensitivity in obese women

Knockdown of SP1/Syncytin1 axis inhibits the proliferation and metastasis through the AKT and ERK1/2 signaling pathways in non‐small cell lung cancer

Genetic variants in the TORC2 gene promoter and their association with body measurement and carcass quality traits in Qinchuan cattle

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