Long non-coding RNA HCP5 serves as a ceRNA sponging miR-17-5p and miR-27a/b to regulate the pathogenesis of childhood obesity via the MAPK signaling pathway

2019 ◽  
Vol 32 (12) ◽  
pp. 1327-1339 ◽  
Author(s):  
Rui Chen ◽  
Guangda Xin ◽  
Xiaofei Zhang
Keyword(s):  
Childhood Obesity ◽  
Signaling Pathway ◽  
Human Leukocyte ◽  
Microarray Dataset ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Differentially Expressed ◽  
Mitogen Activated Protein Kinase ◽  
Messenger Rnas ◽  
Tissue Samples

Abstract Background This study aimed to investigate the completing endogenous RNA (ceRNA) network involved in childhood obesity. Methods The microarray dataset GSE9624 was downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed long non-coding RNAs (lncRNAs) (DELs) and messenger RNAs (DEMs) were isolated between the childhood obesity and non-obesity tissue samples. Then, Gene Ontology (GO) functional and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of isolated DEMs were performed. DELs and DEMs targeted miRNAs were predicted to construct a ceRNA regulatory network. Finally, critical lncRNAs were validated in another dataset. Results A total of 1257 differentially expressed RNAs were screened, including 28 lncRNAs and 1229 mRNAs. In addition, these RNAs were mainly involved in defense response, cell cycle, mitogen-activated protein kinase (MAPK) signaling pathway, apoptosis, etc. Three lncRNAs (human leukocyte antigen complex 5 [HCP5], long intergenic non-protein coding RNA 839 [LINC00839] and receptor activity modifying protein 2 [RAMP2-AS1]) and two related miRNAs (hsa-miR-17-5p and hsa-miR-27a/b-3p) were identified as key RNAs in childhood obesity. Specifically, lncRNA HCP5 interacted with miR-17-5p and miR-27a/b to regulate nemo-like kinase (NLK) and Ras-related protein 2 (RRAS2) via the MAPK signaling pathway. Finally, four genes (RRAS2, NLK, bcl2/adenovirus E1B protein-interacting protein 3 [BNIP3] and phorbol-12-myristate-13-acetate-induced protein 1 [PMAIP1]) targeted by miRNAs were predicted as critical genes and might be novel diagnostic biomarkers of childhood obesity. Conclusions lncRNA HCP5 could serve as a ceRNA sponging miR-17-5p and miR-27a/b to regulate the pathogenesis of childhood obesity via NLK and RRAS2 in the MAPK signaling pathway.

scholarly journals Bu Shen Zhu Yun Decoction Improves Endometrial Receptivity via VEGFR-2-Mediated Angiogenesis

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Li Li ◽  
Huabo Jiang ◽  
Xuecong Wei ◽  
Dandan Geng ◽  
Ming He ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Embryo Implantation ◽  
Mapk Signaling ◽  
Endometrial Receptivity ◽  
Mapk Signaling Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Cell Counting ◽  
Nuclear Antigen ◽  
Vitro Fertilization

Vascular endothelial growth factor receptor-2 (VEGFR-2) regulates the mitogen-activated protein kinase (MAPK) signaling pathway and plays an important role in angiogenesis. Bu Shen Zhu Yun decoction (BSZYD) can improve endometrial receptivity and embryo implantation rates in patients undergoing in vitro fertilization. However, whether BSZYD improves endometrial receptivity via angiogenesis remains unclear. Here, we investigated the effects of BSZYD on the proliferation, migration, and angiogenesis of human endometrial microvascular endothelial cells (HEMECs) and found that BSZYD upregulated the expression of cyclin D1, matrix metalloproteinase 9 (MMP9), and proliferating cell nuclear antigen (PCNA) in HEMECs. Cell Counting Kit 8 assay, scratch-wound assay, and Tube Formation Assay results showed that BSZYD promoted the proliferation, migration, and angiogenesis of HEMECs. Western blot analysis results revealed the activation of the MAPK signaling pathway by BSZYD through the upregulation of VEGF and VEGFR-2 expression. Together, these findings highlight the novel mechanism underlying BSZYD-mediated improvement in endometrial receptivity through the MAPK signaling pathway.

scholarly journals Comparative analysis of gene expression profiles in differentiated subcutaneous adipocytes between Jiaxing Black and Large White Pigs

2020 ◽  
Author(s):  
Dawei Zhang ◽  
Wenjing Wu ◽  
Xin Huang ◽  
Ke Xu ◽  
Cheng Zheng ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Expression Profiles ◽  
Mapk Signaling ◽  
Fat Deposition ◽  
Mapk Signaling Pathway ◽  
Differentially Expressed ◽  
Rna Seq ◽  
Domestic Pig ◽  
Large White ◽  
Pig Breeds

Abstract Background: Chinese domestic pig breeds are reputed for pork quality, but their low ratio of lean-to-fat carcass weight decreases production efficiency. A better understanding of the genetic regulation network of SC fat tissue is necessary for the rational selection of Chinese domestic pig breeds. In the present study, SC adipocytes were isolated from Jiaxing Black pigs (a Chinese indigenous pig breed with redundant SC fat deposition) and Large White pigs (a lean-type pig breed with relatively low SC fat deposition) and the expression profiles of mRNAs and lncRNAs were compared by RNA-seq analysis to identify biomarkers correlated with the differences of SC fat deposition between the two breeds.Results: A total of 3,371 differentially expressed genes (DEGs) and 1,182 differentially expressed lncRNAs (DELs) were identified in SC adipocytes between Jiaxing Black (JX) and Large White (LW) pigs, which included 797 upregulated mRNAs, 2,574 downregulated mRNAs, 461 upregulated lncRNAs and 721 downregulated lncRNAs. Gene Ontology and KEGG pathway analyses revealed that the DEGs and DELs were mainly involved in the immune response, cell fate determination, PI3K-Akt signaling pathway and MAPK signaling pathway, which are known to be related to adipogenesis and lipid metabolism. The expression levels of DEGs and DELs according to the RNA-seq data were verified by quantitative PCR, which showed 81.8% consistency. The differences in MAPK pathway activity between JX and LW pigs was confirmed by western blot analysis, with <100-fold elevated p38 phosphorylation in JX pigs.Conclusions: This study offers a detailed characterization of mRNAs and lncRNAs in fat- and lean-type pig breeds. The activity of the MAPK signaling pathway was found to be associated with subcutaneous adipogenesis. These results greatly enhance our understanding of the molecular mechanisms regulating SC fat deposition in pigs.

scholarly journals The oxygenated products of cryptotanshinone by biotransformation with Cunninghamella elegans exerting anti-neuroinflammatory effects by inhibiting TLR 4-mediated MAPK signaling pathway

2020 ◽  
Author(s):  
Jing-Shuai Wu ◽  
Qin-Yu Meng ◽  
Xiao-Hui Shi ◽  
Zhen-Kun Zhang ◽  
Hua-Shi Guan ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Transcriptome Analysis ◽  
Salvia Miltiorrhiza ◽  
Underlying Mechanism ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Cunninghamella Elegans ◽  
Chinese Medicinal Herb ◽  
Oxygenated Products

Abstract Background: Neuroinflammatory processes are critical in the development and progression of Alzheimer's disease (AD). The potent anti-neuroinflammatory inhibitors are expected as the candidates to treat AD. Cryptotanshinone (1), a major bioactive constituent in the traditional Chinese medicinal herb Dan-Shen Salvia miltiorrhiza Bunge, has been reported to possess remarkable pharmacological activities, especially anti-oxidation and anti-inflammation. Methods: Cryptotanshinone (1) was biotransformed with the fungus Cunninghamella elegans AS3.2028 to improve its bioactivities and physicochemical properties. The structures of transformed products were elucidated by comprehensive spectroscopic analysis including HRESIMS, NMR and ECD data. Their anti-neuroinflammatory activities were assessed by ELISA, transcriptome analysis, western blot, and immunofluorescence methods. Results: Three oxygenated products (2–4) at C-3 of cryptotanshinone (1) were obtained, among them 2 was a new compound. All of the biotransformed products (2–4) were found to inhibit significantly lipopolysaccharide-induced nitric oxide production in BV2 microglia cells with the IC50 values of 0.16‒1.16 μM, approximately 2‒20 folds stronger than the substrate (1). These biotransformed products also displayed remarkably improved inhibitory effects on the production of inflammatory cytokines (IL-1β, IL-6, TNF-α, COX-2 and iNOS) in BV-2 cells via targeting TLR4 compared to substrate (1). The underlying mechanism of 2 was elucidated by comparative transcriptome analysis, which suggested that it reduced neuroinflammatory mainly through mitogen-activated protein kinase (MAPK) signaling pathway. Western blotting results revealed that 2 downregulated LPS-induced phosphorylation of JNK, ERK, and p38 in MAPK signaling pathway. Conclusion: The biotransformed products of cryptotanshinone exhibit potent anti-neuroinflammatory activities. These findings provide a basal material for the discovery of candidates in treating AD.

scholarly journals Proteomic Analysis of Radiation-Induced Acute Liver Damage in a Rabbit Model

Dose-Response ◽  
2019 ◽  
Vol 17 (4) ◽  
pp. 155932581988950 ◽  
Author(s):  
Lingong Jiang ◽  
Huimin Jia ◽  
Zhicheng Tang ◽  
Xiaofei Zhu ◽  
Yangsen Cao ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Liver Damage ◽  
Rabbit Model ◽  
Mapk Signaling ◽  
Differentially Expressed ◽  
Mitogen Activated Protein Kinase ◽  
Differentially Expressed Proteins ◽  
Label Free ◽  
Radiation Induced ◽  
Liver Tissues

Radiation-induced liver damage (RILD) has become a limitation in radiotherapy for hepatocellular carcinoma. We established a rabbit model of RILD by CyberKnife. Electron microscopy analysis revealed obvious nuclear atrophy and disposition of fat in the nucleus after irradiation. We then utilized a mass spectrometry-based label-free relative quantitative proteomics approach to compare global proteomic changes of rabbit liver in response to radiation. In total, 2365 proteins were identified, including 338 proteins that were significantly dysregulated between irradiated and nonirradiated liver tissues. These differentially expressed proteins included USP47, POLR2A, CSTB, MCFD2, and CSNK2A1. Real-time polymerase chain reaction confirmed that USP47 and CABLES1 transcripts were significantly higher in irradiated liver tissues, whereas MCFD2 and CSNK2A1 expressions were significantly reduced. In Clusters of Orthologous Groups of proteins analysis, differentially expressed proteins were annotated and divided into 24 categories, including posttranslational modification, protein turnover, and chaperones. Kyoto Encyclopedia of Genes and Genomes analysis revealed that the enriched pathways in dysregulated proteins included the vascular endothelial growth factors (VEGF) signaling pathway, the mitogen-activated protein kinase (MAPK) signaling pathway, and the adipocytokine signaling pathway. The identification of proteins and pathways is crucial toward elucidating the radiation response process of the liver, which may facilitate the discovery of novel therapeutic targets.

scholarly journals Targeting ERK-Hippo Interplay in Cancer Therapy

2020 ◽  
Vol 21 (9) ◽  
pp. 3236 ◽  
Author(s):  
Karel Vališ ◽  
Petr Novák
Keyword(s):  
Cancer Therapy ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Cross Talk ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Cancer Therapies ◽  
Anti Cancer ◽  
Targeted Inhibition

Extracellular signal-regulated kinase (ERK) is a part of the mitogen-activated protein kinase (MAPK) signaling pathway which allows the transduction of various cellular signals to final effectors and regulation of elementary cellular processes. Deregulation of the MAPK signaling occurs under many pathological conditions including neurodegenerative disorders, metabolic syndromes and cancers. Targeted inhibition of individual kinases of the MAPK signaling pathway using synthetic compounds represents a promising way to effective anti-cancer therapy. Cross-talk of the MAPK signaling pathway with other proteins and signaling pathways have a crucial impact on clinical outcomes of targeted therapies and plays important role during development of drug resistance in cancers. We discuss cross-talk of the MAPK/ERK signaling pathway with other signaling pathways, in particular interplay with the Hippo/MST pathway. We demonstrate the mechanism of cell death induction shared between MAPK/ERK and Hippo/MST signaling pathways and discuss the potential of combination targeting of these pathways in the development of more effective anti-cancer therapies.

scholarly journals MKP-1 reduces Aβ generation and alleviates cognitive impairments in Alzheimer’s disease models

2019 ◽  
Vol 4 (1) ◽  
Author(s):  
Yehong Du ◽  
Yexiang Du ◽  
Yun Zhang ◽  
Zhilin Huang ◽  
Min Fu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Signaling Pathway ◽  
Amyloid Β ◽  
Gene Promoter ◽  
Long Term Potentiation ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Negative Regulator ◽  
Mitogen Activated Protein Kinase

AbstractMitogen-activated protein kinase (MAPK) phosphatase 1 (MKP-1) is an essential negative regulator of MAPKs by dephosphorylating MAPKs at both tyrosine and threonine residues. Dysregulation of the MAPK signaling pathway has been associated with Alzheimer’s disease (AD). However, the role of MKP-1 in AD pathogenesis remains elusive. Here, we report that MKP-1 levels were decreased in the brain tissues of patients with AD and an AD mouse model. The reduction in MKP-1 gene expression appeared to be a result of transcriptional inhibition via transcription factor specificity protein 1 (Sp1) cis-acting binding elements in the MKP-1 gene promoter. Amyloid-β (Aβ)-induced Sp1 activation decreased MKP-1 expression. However, upregulation of MKP-1 inhibited the expression of both Aβ precursor protein (APP) and β-site APP-cleaving enzyme 1 by inactivating the extracellular signal-regulated kinase 1/2 (ERK)/MAPK signaling pathway. Furthermore, upregulation of MKP-1 reduced Aβ production and plaque formation and improved hippocampal long-term potentiation (LTP) and cognitive deficits in APP/PS1 transgenic mice. Our results demonstrate that MKP-1 impairment facilitates the pathogenesis of AD, whereas upregulation of MKP-1 plays a neuroprotective role to reduce Alzheimer-related phenotypes. Thus, this study suggests that MKP-1 is a novel molecule for AD treatment.

Inhibition of miR-200c Expression Promotes Activation of Extracellular Signal-Regulated Kinase (ERK)/ Mitogen-Activated Protein Kinase (MAPK) Signaling Pathway and Inhibits Osteogenic Differentiation in Osteoporosis Mice

2020 ◽  
Vol 10 (2) ◽  
pp. 163-168
Author(s):  
Sheng Wang ◽  
Zhonghan Min ◽  
Run Gu ◽  
Zhongwei Yu ◽  
Pingquan Chen ◽  
...  
Keyword(s):  
Osteogenic Differentiation ◽  
Signaling Pathway ◽  
Mapk Signaling ◽  
Bone Diseases ◽  
Mapk Signaling Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Erk Mapk ◽  
Mitogen Activated Protein ◽  
Marrow Mesenchymal Stem Cells ◽  
Sirna Group

During OP bone metabolism, activated MAPK signaling can promote the proliferation and differentiation of osteoclasts. miRNAs involve in bone diseases. Our study aimed to evaluate miR-200c’s effect on ERK/MAPK signaling pathway in OP. miR-200c expression in OP mice and normal mice was detected by qPCR. BMSCs were cultured and transfected with siRNA to establish a miR-200c knockout model. Flow cytometry was used to detect cell apoptosis and ERK/MAPK signaling protein was detected by Western blot. miR-200c expression in OP mice was significantly lower than that in normal mice. Bone marrow mesenchymal stem cells (BMSCs) contain a large amount of siRNA particles under a fluorescence microscope. siRNA transfection can effectively inhibit miR-200c expression without difference of BMSCs apoptosis between miR-200c siRNA group and NC group. However, ERK1/2 and P38 expression in experimental group were significantly higher than those in NC siRNA group with reduced ALP activity. In addition, BMSCs osteogenic differentiation was further diminished when miR-200c expression was inhibited. miR-200c expression is lower in OP mice. miR-200c siRNA inhibits BMSCs osteogenic differentiation via ERK/MAPK signaling, thereby promoting OP progression.

scholarly journals Aloesin Suppresses Cell Growth and Metastasis in Ovarian Cancer SKOV3 Cells through the Inhibition of the MAPK Signaling Pathway

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Li-qian Zhang ◽  
Rong-wei Lv ◽  
Xiang-dong Qu ◽  
Xian-jun Chen ◽  
Hong-sheng Lu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Growth ◽  
Signaling Pathway ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Migration And Invasion ◽  
Therapeutic Drug ◽  
Dependent Manner ◽  
Skov3 Cells

Aloesin is an active constituent of the herb aloe vera and plays a crucial role in anti-inflammatory activity, ultraviolet protection, and antibacterium. We investigated the role and possible mechanisms of aloesin in the cell growth and metastasis of ovarian cancer. It was found that aloesin inhibited cell viability and cell clonality in a dose-dependent manner. It arrests the cell cycle at the S-phase and induced apoptosis in SKOV3 cells. In an in vivo experiment, it was observed that aloesin inhibited tumor growth. Moreover, it inhibited migration and invasion of cancer in SKOV3 cells. Interestingly, members from the mitogen-activated protein kinase (MAPK) signaling family became less phosphorylated as the aloesin dose increased. This suggests that aloesin exerts its anticancer effect through the MAPK signaling pathway. Our data also highlights the possibility of using aloesin as a novel therapeutic drug for ovarian cancer treatment.

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