Osthole inhibits cell proliferation by regulating the TGF-β1/Smad/p38 signaling pathways in pulmonary arterial smooth muscle cells

Yue, Yun; Li, Yiqi; Fu, Shu; Wu, Yuting; Zhu, Ling; Hua, Liang; Lv, Junyuan; Li, Yeli; Yang, Dan

doi:10.1016/j.biopha.2019.109640

Cited by 29 publications

(26 citation statements)

References 44 publications

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“…It also inhibits Smad3 transcriptional activity by promoting Smad3 phosphorylation in a cell cycledependent manner [17]. In our study, we found that iso avone signi cantly decreased cyclin D1 expression levels in ovarian and breast cancer cell lines.…”

Section: Discussionsupporting

confidence: 52%

Isoflavones Appeared Different Effects In The Presence of Different Concentrations of Estrogen In Ovarian And Endometrial Cancer Cells

Shi

Wei

et al. 2021

Preprint

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Background: Epithelial ovarian cancer and breast cancer are common gynecological malignancies with a high mortality rate. Isoflavone is a phytoestrogen that is ubiquitous in food and Chinese herbs. Although many epidemiological studies have shown that ingestion of isoflavones can reduce the risk of ovarian and breast cancer, its cellular functions and underlying mechanisms remain unclear. Methods: This study used isoflavones to treat SKOV-3 (ovarian cancer) and MCF-7 (breast cancer) cell lines with high estrogen levels. Cell counting and MTS assays were used to detect cell proliferation and viability. Quantitative PCR and western blotting were performed to investigate the expression levels of cell cycle factors. Results: The results showed that isoflavones inhibited cell proliferation and viability in SKOV-3 and MCF-7 cells under high estrogen levels. After isoflavone treatment, PCNA, CDK4, and cyclin D1 expression levels were significantly decreased, but p21 and p27 expression levels were significantly increased. Conclusion: Isoflavones could inhibit cell proliferation within high levels of estrogen in ovarian and breast cancer cells. These findings will provide a new theory for gynecological malignancy therapy.

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Section: Discussionsupporting

confidence: 52%

Isoflavones Appeared Different Effects In The Presence of Different Concentrations of Estrogen In Ovarian And Endometrial Cancer Cells

Shi

Wei

et al. 2021

Preprint

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“…lncRNAs are a class of non-coding RNAs with a length of >200 nucleotides, which are involved in various regulatory processes, such as transcriptional silencing, transcriptional activation, chromosome modification and intra nuclear transport ( 22 , 23 ). It has previously been reported that lncRNAs are closely associated with the occurrence, development, prevention and treatment of CAD ( 24 , 25 ).…”

Section: Introductionmentioning

confidence: 99%

Knockdown of mesenchymal stem cell‑derived exosomal LOC100129516 suppresses the symptoms of atherosclerosis via upregulation of the PPARγ/LXRα/ABCA1 signaling pathway

Zhang

Han

et al. 2021

Int J Mol Med

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Mesenchymal stem cell (MSC) therapy has potential applications in treating atherosclerosis and coronary heart disease (CAD). Previous studies have demonstrated that MSCs are the most preferable sources of therapeutic exosomes, which carry long non-coding RNAs and participate in the progression of atherosclerosis. The results of our previous bioinformatics study demonstrated that the levels of LOC100129516 were significantly upregulated in peripheral blood mononuclear cells obtained from patients with CAD. However, the biological role of LOC100129516 in the development of atherosclerosis remains to be elucidated. In the present study, THP-1 cells were treated with oxidized low-density lipoproteins to induce foam cell formation in vitro . Reverse transcription-quantitative PCR (RT-qPCR) was performed to detect the levels of LOC100129516 in THP-1 macrophage-derived foam cells. In addition, an in vivo model of atherosclerosis was established using Apolipoprotein E (ApoE) knockout (ApoE −/− ) mice. The results of the RT-qPCR assays demonstrated that the levels of LOC100129516 were upregulated in THP-1 macrophage-derived foam cells. MSC-derived exosomes were able to deliver small interfering (si)-LOC100129516 to THP-1 cells to reduce the levels of LOC100129516. Moreover, transfection of si-LOC100129516 via exosomal delivery significantly decreased the levels of total cholesterol (TC), free cholesterol and cholesterol ester in THP-1 macrophage-derived foam cells. Exosomal-mediated delivery of si-LOC100129516 decreased TC levels and low-density lipoprotein levels in the ApoE −/− atherosclerosis mouse model. Mechanistically, exosomal-mediated delivery of si-LOC100129516 promoted cholesterol efflux by activating the peroxisome proliferator-activated receptor γ (PPARγ)/liver X receptor α (LXRα)/phospholipid-transporting ATPase ABCA1 (ABCA1) signaling pathway in vitro and in vivo . Collectively, these results suggested that exosomal-mediated delivery of si-LOC100129516, in which the exosomes were derived from MSCs, promoted cholesterol efflux and suppressed intracellular lipid accumulation, ultimately alleviating the progression of atherosclerosis via stimulation of the PPARγ/LXRα/ABCA1 signaling pathway.

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“…Decreased CDK2 expression can block cell cycle progression and inhibit the proliferation of pulmonary artery smooth muscle cells. Proliferative PASMCs exist in PAH patients and are closely related to vascular remodeling ( Yue et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of Hub Genes and MicroRNAs Associated With Idiopathic Pulmonary Arterial Hypertension by Integrated Bioinformatics Analyses

et al. 2021

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ObjectiveThe aim of this study is the identification of hub genes associated with idiopathic pulmonary arterial hypertension (IPAH).Materials and MethodsGSE15197 gene expression data was downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified by screening IPAH patients and controls. The 5,000 genes with the greatest variances were analyzed using a weighted gene co-expression network analysis (WGCNA). Modules with the strongest correlation with IPAH were chosen, followed by a functional enrichment analysis. Protein–protein interaction (PPI) networks were constructed to identify hub gene candidates using calculated degrees. Real hub genes were found from the overlap of DEGs and candidate hub genes. microRNAs (miRNAs) targeting real hub genes were found by screening miRNet 2.0. The most important IPAH miRNAs were identified.ResultsThere were 4,395 DEGs identified. WGCNA indicated that green and brown modules associated most strongly with IPAH. Functional enrichment analysis showed that green and brown module genes were mainly involved in protein digestion and absorption and proteoglycans in cancer, respectively. The top ten candidate hub genes in green and brown modules were identified, respectively. After overlapping with DEGs, 11 real hub genes were identified: EP300, MMP2, CDH2, CDK2, GNG10, ALB, SMC2, DHX15, CUL3, BTBD1, and LTN1. These genes were expressed with significant differences in IPAH versus controls, indicating a high diagnostic ability. The miRNA–gene network showed that hsa-mir-1-3p could associate with IPAH.ConclusionEP300, MMP2, CDH2, CDK2, GNG10, ALB, SMC2, DHX15, CUL3, BTBD1, and LTN1 may play essential roles in IPAH. Predicted miRNA hsa-mir-1-3p could regulate gene expression in IPAH. Such hub genes may contribute to the pathology and progression in IPAH, providing potential diagnostic and therapeutic opportunities for IPAH patients.

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Osthole inhibits cell proliferation by regulating the TGF-β1/Smad/p38 signaling pathways in pulmonary arterial smooth muscle cells

Cited by 29 publications

References 44 publications

Isoflavones Appeared Different Effects In The Presence of Different Concentrations of Estrogen In Ovarian And Endometrial Cancer Cells

Isoflavones Appeared Different Effects In The Presence of Different Concentrations of Estrogen In Ovarian And Endometrial Cancer Cells

Knockdown of mesenchymal stem cell‑derived exosomal LOC100129516 suppresses the symptoms of atherosclerosis via upregulation of the PPARγ/LXRα/ABCA1 signaling pathway

Identification of Hub Genes and MicroRNAs Associated With Idiopathic Pulmonary Arterial Hypertension by Integrated Bioinformatics Analyses

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