Notch3 promotes 3T3‐L1 pre‐adipocytes differentiation by up‐regulating the expression of LARS to activate the mTOR pathway

Guo, Yuxian; Tan, Junyu; Xiong, Wei; Chen, Shuzhao; Fan, Liping; Li, Yaochen

doi:10.1111/jcmm.14849

Cited by 11 publications

(9 citation statements)

References 37 publications

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“…The same result was observed in the rescue experiment of this study. Also, the same problem has been found in previous studies ( Guo et al, 2020 ; Xu et al, 2021 ; Chen et al, 2022 ). In addition, pref-1 , a well-known negative regulator of adipogenesis, was positively correlated with miR130b duplex (miR-130b-3p and miR-130b-5p) and KLF3 regulated goat intramuscular adipocyte differentiation.…”

Section: Discussionsupporting

confidence: 86%

miR-130b duplex (miR-130b-3p/miR-130b-5p) negatively regulates goat intramuscular preadipocyte lipid droplets accumulation by inhibiting Krüppel-like factor 3 expression

et al. 2023

Journal of Animal Science

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Intramuscular lipid deposition is important for meat quality improvement. microRNAs and their target mRNAs provide a new approach for studying the mechanism of fat deposition. The present study aimed to investigate the effect of miR-130b duplex (miR-130b-5p, miR-130b-3p) and its target gene KLF3 in regulating goat intramuscular adipocyte differentiation. Goat intramuscular preadipocytes were isolated from 7-day-old male Jianzhou big ear goats and identified by Oil red O staining after differentiation induction. miR-130b-5p and miR-130b-3p mimics or inhibitors and their corresponding controls were transfected into goat intramuscular preadipocytes respectively and differentiation was induced by 50μM oleic acid for 48h. Oil red O and Bodipy staining indicated that both miR-130b-5p and miR-130b-3p can reduce lipid droplets accumulation and triglyceride (TG) content (P < 0.01). Differentiation markers C/EBPα, C/EBPβ, PPARγ, pref1, fatty acids synthesis markers ACC, FASN, DGAT1, DGAT2, AGPAT6, TIP47, GPAM, ADRP, AP2, SREBP1 and TG markers LPL, ATGL, HSL were assessed by qPCR. All the markers measured were downregulated by miR-130b-5p and miR-130b-3p analog (P < 0.01), suggesting that miR-130b inhibits goat intramuscular adipocyte adipogenic differentiation, fatty acids synthesis and lipid lipolysis. To examine the mechanism of miR-130b duplex inhibition of lipid deposition, TargetScan, miRDB and starBase were used to predict the potential targets, KLF3 was found to be the only one intersection. Furthermore, the 3'UTR of KLF3 was cloned, qPCR analysis and dual luciferase activity assay showed that both miR-130b-5p and miR-130b-3p could directly regulate KLF3 expression (P < 0.01). In addition, overexpression and interference of KLF3 was conducted, it was found that KLF3 positively regulated lipid droplets accumulation by Oil red O, Bodipy staining and TG content detection (P < 0.01). Quantitative PCR result indicated that KLF3 overexpression promoted lipid droplets accumulation relative genes C/EBPβ, PPARγ, pref1, ACC, FASN, DGAT1, DGAT2, AGPAT6, TIP47, GPAM, ADRP, SREBP1, LPL and ATGL expression (P < 0.01). Downregulation of KLF3 inhibited the expression of genes such as C/EBPα, C/EBPβ, PPARγ, pref1, TIP47, GPAM, ADRP, AP2, LPL and ATGL expression (P < 0.01). Taken together, these results indicate that miR-130b duplex could directly inhibit KLF3 expression, then attenuated adipogenic and TG synthesis genes expression, thus leading to its anti-adipogenic effect.

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Section: Discussionsupporting

confidence: 86%

miR-130b duplex (miR-130b-3p/miR-130b-5p) negatively regulates goat intramuscular preadipocyte lipid droplets accumulation by inhibiting Krüppel-like factor 3 expression

et al. 2023

Journal of Animal Science

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“…For example, in breast cancer, NOTCH3 trans-activates PTEN by binding a CSL binding element in PTEN promoter 38 . NOTCH3 promotes adipocyte differentiation of 3T3-L1 preadipocytes by directly up-regulating LARS expression and activating the mTOR pathway 39 . That indicates that NOTCH3 may not directly negatively regulate the expression of ZEB1.…”

Section: Discussionmentioning

confidence: 99%

NOTCH3 inhibits transcription factor ZEB1 expression and metastasis of breast cancer cells via transcriptionally upregulating miR-223

Chen,

Zhong,

et al. 2024

J. Cancer

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Background: NOTCH receptor 3 (NOTCH3) and zinc finger E-box binding protein 1 (ZEB1) play important roles in breast cancer respectively. NOTCH3 maintains the luminal phenotype and inhibits epithelial-mesenchymal transition (EMT) in breast cancer, while ZEB1 and NOTCH3 have the opposite effects. Methods: Public databases were used to predict the expression of NOTCH3 and ZEB1 in breast cancer cell lines. The regulatory effect of NOTCH3 on ZEB1 expression was verified by western blot and RT-PCR. MiRNAs regulating ZEB1 expression were identified by using multiple databases and confirmed by reporter gene experiments. Cellular function experiments were conducted to evaluate the role of NOTCH3/miR-223/ZEB1 in the proliferation and invasion of triple-negative breast cancer (TNBC). Results: NOTCH3 and ZEB1 have opposite expression pattern in MCF-7 cells that over-express LncATB or were incubated in TGF-β to induce EMT. Western blotting and RT-PCR showed that NOTCH3 could regulate expression of ZEB1. MiR-223 inhibited the proliferation and invasion of breast cancer cells via down-regulating the expression of ZEB1. NOTCH3 inhibited the proliferation and invasion of breast cancer cells via up-regulating the expression of miR-223. Clinically, high expression of NOTCH3, miR-223 or low expression of ZEB1 were related to good prognosis of breast cancer patients. Conclusion: The current study reports a novel NOTCH3/miR-223/ZEB1 axis, which can inhibit the proliferation and invasion of breast cancer cells, and may serve as a potential biomarker for the prognosis of breast cancer.

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“…MYC could induce aberrant choline metabolism by transcriptionally activating the key enzyme phosphate cytidylyltransferase 1 choline-α (PCYT1A) [80]. Minoacyl-tRNA_biosynthesis pathway was significantly influenced by NOTCH3 [81].…”

Section: Discussionmentioning

confidence: 99%

Identification of a 16-MTGs Prognostic Signature in Diffuse Large B-Cell Lymphoma

Wang,

et al. 2024

Analytical Cellular Pathology

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Background. Diffuse large B-cell lymphoma (DLBCL) is one of the largest lymphoma subcategories. Usually, 50%–70% of DLBCL patients can be cured by the standard treatment. But, at least one third have bad prognosis. Based on this situation, the research on DLBCL therapy strategy is still indispensable. Methods. A prognostic signature was built according to the public data and bioinformatics methods, the stability and reliability was assessed and validated. GSEA was performed to explore the difference in different groups. Consensus clustering and immune infiltration analysis were conducted comprehensively. Results. In this work, a signature based on multiple metabolism-associated genes (MTGs) was established, containing 16 MTGs, to predict the prognosis of DLBCL patients. The accuracy and effectiveness of this signature have been verified by three external validation sets. According to the risk formula, DLBCL patients were divided into high- and low-risk groups, and the survival rate of the low-risk group was significantly higher than that of the high-risk group. Furthermore, gene set enrichment analysis (GSEA) demonstrated that beta-alanine metabolism and regulation of actin cytoskeleton signal pathways were enriched in the low-risk group. The actual survival and nomogram-predicted survival matched well both in the training cohort and verification cohorts. Conclusion. In general, our prognostic signature can provide reliable and valuable information for medical workers in predicting the prognosis of DLBCL. A preprint was made available by the research square in the following link: “https://www.researchsquare.com/article/rs-1468741/v2.”

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Notch3 promotes 3T3‐L1 pre‐adipocytes differentiation by up‐regulating the expression of LARS to activate the mTOR pathway

Cited by 11 publications

References 37 publications

miR-130b duplex (miR-130b-3p/miR-130b-5p) negatively regulates goat intramuscular preadipocyte lipid droplets accumulation by inhibiting Krüppel-like factor 3 expression

miR-130b duplex (miR-130b-3p/miR-130b-5p) negatively regulates goat intramuscular preadipocyte lipid droplets accumulation by inhibiting Krüppel-like factor 3 expression

NOTCH3 inhibits transcription factor ZEB1 expression and metastasis of breast cancer cells via transcriptionally upregulating miR-223

Identification of a 16-MTGs Prognostic Signature in Diffuse Large B-Cell Lymphoma

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