Evodiamine inhibits the proliferation of human osteosarcoma cells by blocking PI3K/Akt signaling

Meng, Zijun; Wu, Nanping; Shu, Ke-Jie; Zou, Xiang; Zhang, Ranxi; Pi, Chang-Jun; Ke, Zhen-Yong; Chen, Liang; Deng, Zhong‐Liang; Liang, Yin

doi:10.3892/or.2015.4084

Cited by 43 publications

(25 citation statements)

References 49 publications

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“…GO terms related to translation (e.g., cytoplasmic translation) were also enriched in OS genes. In line with previous studies, several pathways, such as mTOR signaling pathway (ranked 5th) (29,30), Hippo signaling pathway (ranked 9th) (31), PI3K-Akt signaling pathway (ranked 10th) (30,32), MAPK signaling pathway (ranked 11th) (33), Wnt signaling pathway (ranked 22nd) (34,35), p53 signaling pathway (ranked 24th) (36–38), and TGF-β signaling pathway (ranked 27th) (38,39), were enriched in OS genes. In addition, several cancer-related pathways were identified, such as Pathways in cancer, Proteoglycans in cancer, central carbon metabolism in cancer, and transcriptional misregulation in cancer.…”

Section: Resultssupporting

confidence: 89%

Analyzing the disease module associated with osteosarcoma via a network‑ and pathway‑based approach

Zhang

2018

Exp Ther Med

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Osteosarcoma is the most common type of primary malignant bone tumor observed in children and adolescents. The aim of the present study was to identify an osteosarcoma-related gene module (OSM) by looking for a dense module following the integration of signals from genome-wide association studies (GWAS) into the human protein-protein interaction (PPI) network. A dataset of somatic mutations in osteosarcoma was obtained from the dbGaP database and their testing P-values were incorporated into the PPI network from a recent study using the dmGWAS bioconductor package. An OSM containing 201 genes (OS genes) and 268 interactions, which were closely associated with immune response, intracellular signal transduction and cell activity was identified. Topological analysis of the OSM identified 11 genes, including APP, APPBP2, ATXN1, HSP90B1, IKZF1, KRTAP10-1, PAK1, PDPK1, SMAD4, SUZ12 and TP53 as potential diagnostic biomarkers for osteosarcoma. The overall survival analysis of osteosarcoma for those 11 genes based on a dataset from the Cancer Genome Atlas, identified APP, HSP90B1, SUZ12 and IKZF1 as osteosarcoma survival-related genes. The results of the present study should be helpful in understanding the diagnosis and treatment of osteosarcoma and its underlying mechanisms. In addition, the methodology used in the present study may be suitable for the analysis of other types of disease.

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Section: Resultssupporting

confidence: 89%

Analyzing the disease module associated with osteosarcoma via a network‑ and pathway‑based approach

Zhang

2018

Exp Ther Med

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“…Recent evidence has also confirmed that the protein expression of PTEN could be suppressed by microRNAs and PTEN is confirmed to be target for miR-213031. Research also found that PTEN could reduce the phosphorylation of AKT protein32, which was involved in hypertrophic scar formation33. Moreover, the expression of PTEN could be effectively inhibited by TGF-β34.…”

Section: Discussionmentioning

confidence: 90%

TGF-β1 promotes scar fibroblasts proliferation and transdifferentiation via up-regulating MicroRNA-21

Liu

et al. 2016

Sci Rep

141

106

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TGF-β1, upregulated in keloid tissue, promotes the proliferation, collagen formation and differentiation of dermal fibroblasts. miR-21 is one of microRNAs first found in human genome. The aim of our study is to explore the mechanisms of miR-21 in TGF-β1-induced scar fibroblasts proliferation and transdifferentiation. In the present study, first we found that TGF-β1 promoted scar fibroblasts proliferation and transdifferentiation via up-regulating miR-21 expression, which could be attenuated when miR-21 was inhibited. Overexpression of miR-21 had similar effect as TGF-β1 on proliferation and transdifferentiation. Additionally, TGF-β1 increased the expressions and activities of MMP2 and MMP9 in keloid fibroblasts, which was suppressed by miR-21 inhibition. Finally, the results demonstrated that PTEN/AKT signaling pathway played important role in TGF-β1-induced transdifferentiation. In conclusion, our study suggests that TGF-β1 promotes keloid fibroblasts proliferation and transdifferentiation via up-regulation of miR-21 and PTEN/AKT signalling pathway plays important role in this process, which provides a potential theoretical basis for clinical treatment of skin scars.

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“…143B cells were seeded in T25 flasks and treated with the indicated infection rates of AdBMP9 for 48 h. Total RNA was extracted using the TRIzol reagent (Invitrogen, Carlsbad, CA, USA) and used to obtain cDNA templates by reverse transcription (RT). Then, the cDNAs were used as templates for determining the expression of target genes by semi-quantitative PCR (sqPCR), as described (36). The primers for each gene were as follows: GAPDH, F:…”

Section: Reverse Transcription and Polymerase Chain Reaction Analysismentioning

confidence: 99%

“…The detailed method was previously described (36). In brief, subconfluent 143B cells were plated in 6-well plates and treated with the indicated concentrations of ATRA and/or AdBMP9 and/or SB203580.…”

Section: Reverse Transcription and Polymerase Chain Reaction Analysismentioning

confidence: 99%

All-trans retinoic acid restored the osteogenic ability of BMP9 in osteosarcoma through the p38 MAPK pathway

Meng

et al. 2017

International Journal of Oncology

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Abstract. Osteosarcoma (OS) is the most common malignant bone tumour and is considered to be a disease caused by a dysfunction in differentiation. Bone morphogenetic protein 9 (BMP9) is the most potent osteogenic factor in mesenchymal stem cells, but it cannot induce osteogenic differentiation in OS cells; this might be one of the determinants in the pathogenesis of OS. All-trans retinoic acid (ATRA) can induce osteogenic differentiation of OS cells and potentiate BMP9-induced osteogenesis in preadipocytes. However, the concomitant effect of ATRA and BMP9 in OS cells is unclear; therefore, in the present study, we focused on this topic. The results showed that BMP9 significantly promoted the proliferation of human OS 143B cells and did not induce osteogenic differentiation of cells in vitro (p<0.01). ATRA inhibited proliferation and induced osteogenesis in 143B cells; these effects could be enhanced by BMP9 overexpression (p<0.05). ATRA could significantly increase the level of phosphorylated p38 MAPK (p-p38) in 143B cells, while BMP9 did not have any significant effect. Notably, BMP9 overexpression enhanced the ability of ATRA to increase the levels of p-p38. Both the osteogenic differentiation and the anti-proliferative activity of BMP9 in the presence of ATRA decreased upon treatment with a specific inhibitor of p38 MAPK (SB203580) (p<0.01). This study indicates that the osteogenic differentiation ability of BMP9 in 143B cells can be restored by ATRA, and the combination of BMP9 and ATRA generated a stronger anti-proliferative effect on 143B cells than ATRA alone. This result may be due to the activation of the p38 MAPK pathway.

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Evodiamine inhibits the proliferation of human osteosarcoma cells by blocking PI3K/Akt signaling

Cited by 43 publications

References 49 publications

Analyzing the disease module associated with osteosarcoma via a network‑ and pathway‑based approach

Analyzing the disease module associated with osteosarcoma via a network‑ and pathway‑based approach

TGF-β1 promotes scar fibroblasts proliferation and transdifferentiation via up-regulating MicroRNA-21

All-trans retinoic acid restored the osteogenic ability of BMP9 in osteosarcoma through the p38 MAPK pathway

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