The Prognostic Significance of Src and p-Src Expression in Patients with Osteosarcoma

Hu, Chao; Deng, Zhouming; Zhang, Yi; Yan, Lei; Cai, Lin; Jun, Lei; Xie, Yuanlong

doi:10.12659/msm.892803

Cited by 17 publications

(11 citation statements)

References 35 publications

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“…Osteosarcoma (OS) is an important cause of cancer-correlated deaths worldwide. OS progression is a complex, multistep process involving numerous abnormal genes and proteins [ 20 , 21 ]. The combination of local radiotherapy/chemotherapy and surgery is currently the main anti-tumor therapy, but treatment fails in many patients, in part due to resistance to chemotherapeutic agents [ 22 , 23 ].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-184 Modulates Doxorubicin Resistance in Osteosarcoma Cells by Targeting BCL2L1

Lin

Huang

et al. 2016

Med Sci Monit

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Background:Early metastasis of osteosarcoma (OS) is highly lethal and responds poorly to drug and radiation therapies. MicroRNAs (miRNAs) are a class of small noncoding RNAs that modulate gene expression at the post-transcriptional level. However, the detailed functions of specific miRNAs are not entirely understood. The aim of the present study was to investigate the role of miR-184 as a mediator of drug resistance in human osteosarcoma. Material/Methods:qRT-PCR was used to analyze the expression level of miR-184 in OS cell line U-2 OS and MG-63 treated with doxorubicin. MiR-184 agomir or miR-184 antagomir was transferred into cells to regulated miR-184. The target of miR-184 was predicted by TargetScan and confirmed by luciferase reporter assay. Bcl-2-like protein 1 (BCL2L1) expression was detected by Western blot. Cell apoptosis was determined by Annexin V staining and analysis by flow cytometry. Results:Doxorubicin induced time-dependent expression of miR-184 in OS cell line U-2 OS and MG-63. Luciferase reporter assay identified BCL2L1 as the direct target gene of miR-184. Furthermore, doxorubicin reduced BCL2L1 expression, which was reversed by miR-184 overexpression and further decreased by miR-184 inhibition in OS cells. In addition, miR-184 agomir reduced doxorubicin-induced cell apoptosis, whereas miR-184 antagomir enhanced apoptosis in OS cells, suggesting that up-regulation of miR-184 contributes to chemoresistance of the OS cell line. Conclusions:Our data show that miR-184 was up-regulated in OS patients treated with doxorubicin therapy and leads to poor response to drug therapy by targeting BCL2L1.

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Section: Discussionmentioning

confidence: 99%

MicroRNA-184 Modulates Doxorubicin Resistance in Osteosarcoma Cells by Targeting BCL2L1

Lin

Huang

et al. 2016

Med Sci Monit

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“…Src kinase activation is considered a prometastatic pathway in several types of tumors, since vital oncogenic mechanisms such as cell proliferation, resistance to apoptosis, invasion and adhesion are involved in it ( 42 ). p-Src expression was revealed to be high in osteosarcoma tissue (64.7%) and was significantly associated with metastasis and clinical stage ( 43 ). Notably, Src kinase activation was frequently detected in anoikis-resistant osteosarcoma cells, and its activation was associated with angiogenesis through increased proangiogenic factor expression, e.g., VEGF-A and IL-8 ( 19 , 21 ).…”

Section: Discussionmentioning

confidence: 99%

Anoikis‑resistant human osteosarcoma cells display significant angiogenesis by activating the Src kinase‑mediated MAPK pathway

Ziran

Zhao

et al. 2018

Oncol Rep

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Tumor cells must resist anoikis to metastasize. There is a key role of angiogenesis in the growth and metastasis of tumors. However, the relationship between anoikis resistance and angiogenesis has not been well explored in human osteosarcoma. In the present study, we reported the higher expression of vascular endothelial growth factor-A (VEGF-A) in osteosarcoma cells that were resistant to anoikis than in parental osteosarcoma cells, promoting the proliferation, tube formation, and migration of human umbilical vein endothelial cells (HUVECs). Src, JNK (Jun amino-terminal kinase) and ERK (extracellular signal-regulated kinase) signaling pathway phosphorylation was activated in anoikis-resistant cells; Src inhibitor reduced the expression of VEGF-A and angiogenesis and inhibited JNK and ERK pathway activity. Overexpression of phosphorylated (p)-Src and VEGF-A was positively correlated to the metastatic potential in human osteosarcoma tissues, as quantified by immunohistochemistry. In addition, p-Src expression was directly correlated with VEGF-A expression and microvessel density in vivo. Our findings revealed that anoikis resistance in osteosarcoma cells increased the expression of VEGF-A and angiogenesis through the Src/JNK/ERK signaling pathways. Thus, Src may be a potential therapeutic alternative in osteosarcoma angiogenesis and metastasis.

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“…SRC is involved in regulating cellular signaling, which results in the migration and invasion of cancer cells (22). In addition, evidence shows that SRC is a prognostic gene for tumors in osteosarcoma (23). In the present study, genes in the PPI network with a high rank in terms of their topological properties were considered to be causal genes for osteosarcoma.…”

Section: Discussionmentioning

confidence: 99%

Identification of characteristic gene modules of osteosarcoma using bioinformatics analysis indicates the possible molecular pathogenesis

Peng

et al. 2017

Molecular Medicine Reports

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The aim of the present study was to investigate the possible pathogenesis of osteosarcoma using bioinformatics analysis to examine gene-gene interactions. A total of three datasets associated with osteosarcoma were downloaded from the Gene Expression Omnibus. The differentially expressed genes (DEGs) were identified using the significance analysis of microarrays method, which then were subjected to the Human Protein Reference Database to identify the protein-protein interaction (PPI) pairs and to construct a PPI network of the DEGs. Subsequent multilevel community analysis was applied to mine the modules in the network, followed by screening of the differential expression module using the GlobalAncova package. The genes in the differential expression modules were verified in the valid datasets. The verified genes underwent functional and pathway enrichment analysis. A total of 616 DEGs were selected to construct the PPI network, which included 5,808 osteosarcoma-specific interaction pairs and 8,012 normal-specific pairs. Tumor protein p53 (TP53), mitogen-activated protein kinase 1 (MAPK1) and estrogen receptor 1 (ESR1) were identified the most important osteosarcoma-associated genes, with the highest levels of topological properties. Neurogenic locus notch homolog protein 3 (NOTCH3) and caspase 1 (CASP1) were identified as the osteosarcoma-specific interaction pairs. Among all 23 mined modules, three were identified as differential expression modules, which were verified in the other two datasets. The genes in these modules were predominantly enriched in the FGFR, MAPK and Notch signaling pathways. Therefore, TP53, MAPK1, ESR1, NOTCH3 and CASP1 may be important in the development of osteosarcoma, and provides valuable clues to investigate the pathogenesis of osteosarcoma using the three differential expression modules.

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The Prognostic Significance of Src and p-Src Expression in Patients with Osteosarcoma

Cited by 17 publications

References 35 publications

MicroRNA-184 Modulates Doxorubicin Resistance in Osteosarcoma Cells by Targeting BCL2L1

MicroRNA-184 Modulates Doxorubicin Resistance in Osteosarcoma Cells by Targeting BCL2L1

Anoikis‑resistant human osteosarcoma cells display significant angiogenesis by activating the Src kinase‑mediated MAPK pathway

Identification of characteristic gene modules of osteosarcoma using bioinformatics analysis indicates the possible molecular pathogenesis

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