High expression levels of Cyr61 and VEGF are associated with poor prognosis in osteosarcoma

Liu, Yanming; Zhang, Feiyue; Zhang, Zhaobo; Wang, Daoqing; Cui, Baojuan; Zeng, Fanshuo; Huang, Laigang; Zhang, Qi; Sun, Qiangsan

doi:10.1016/j.prp.2017.06.004

Cited by 29 publications

(23 citation statements)

References 19 publications

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“…Interestingly, most upregulated angiogenic genes were either well-known angiogenic markers or pro-cancer genes such as VEGFC, CYR61, VASP, EPAS1, JUNB, and CDH13 ( Fig 5F). Recently, it was reported that CYR61, cysteine-rich heparin-binding inducer 61, facilitates angiogenesis and its high expression level is associated with poor prognosis in osteosarcoma (Habel et al, 2015;Liu et al, 2017). We also observed increased expression of CRY61 in endothelial cells treated with sFRP2OE and LFS CM (Figs 5F and G).…”

Section: Secreted Sfrp2 Facilitates Angiogenesis and Tumorigenesis Thsupporting

confidence: 71%

Oncogenic role of sFRP2 in P53-mutant osteosarcoma development via autocrine and paracrine mechanism

Kim

Yoo

Bernitz

et al. 2018

Preprint

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Osteosarcoma (OS), the most common primary bone tumor, is highly metastatic with high chemotherapeutic resistance and poor survival rates. Using induced pluripotent stem cells (iPSCs) generated from Li-Fraumeni syndrome (LFS) patients, we investigated an oncogenic role of secreted frizzled-related protein 2 (sFRP2) in P53 mutation-associated OS development. Interestingly, we found that high sFRP2 expression in OS patient samples correlates with poor survival. Systems-level analyses identified that expression of sFRP2 increases during LFS OS development and can induce angiogenesis. Ectopic sFRP2 overexpression in normal osteoblast precursors is sufficient to suppress normal osteoblast differentiation and to promote OS phenotypes through induction of oncogenic molecules such as FOXM1 and CYR61 in a β-catenin independent manner. Conversely, inhibition of sFRP2, FOXM1 or CYR61 represses the tumorigenic potential. In summary, these findings demonstrate the oncogenic role of sFRP2 in P53 mutation-associated OS development and that inhibition of sFRP2 is a potential therapeutic strategy.

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Section: Secreted Sfrp2 Facilitates Angiogenesis and Tumorigenesis Thsupporting

confidence: 71%

Oncogenic role of sFRP2 in P53-mutant osteosarcoma development via autocrine and paracrine mechanism

Kim

Yoo

Bernitz

et al. 2018

Preprint

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“…5F). High expression levels of CYR61, known to facilitate angiogenesis, were recently associated with poor prognosis in OS (62,63). Interestingly, we also observed increased expression of CYR61 in endothelial cells treated with SFRP2OE and LFS CM ( Fig.…”

Section: Sfrp2oe Dysregulates Ob Differentiation Through Bmp/wntsupporting

confidence: 67%

Oncogenic role of SFRP2 in p53-mutant osteosarcoma development via autocrine and paracrine mechanism

Kim

Yoo

Zhou

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

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Osteosarcoma (OS), the most common primary bone tumor, is highly metastatic with high chemotherapeutic resistance and poor survival rates. Using induced pluripotent stem cells (iPSCs) generated from Li–Fraumeni syndrome (LFS) patients, we investigate an oncogenic role of secreted frizzled-related protein 2 (SFRP2) in p53 mutation-associated OS development. Interestingly, we find that high SFRP2 expression in OS patient samples correlates with poor survival. Systems-level analyses identified that expression of SFRP2 increases during LFS OS development and can induce angiogenesis. Ectopic SFRP2 overexpression in normal osteoblast precursors is sufficient to suppress normal osteoblast differentiation and to promote OS phenotypes through induction of oncogenic molecules such as FOXM1 and CYR61 in a β-catenin–independent manner. Conversely, inhibition of SFRP2, FOXM1, or CYR61 represses the tumorigenic potential. In summary, these findings demonstrate the oncogenic role of SFRP2 in the development of p53 mutation-associated OS and that inhibition of SFRP2 is a potential therapeutic strategy.

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“…It is aberrantly overexpressed in a variety of human malignancies, such as gastric cancer (31), thyroid cancer (32), bladder cancer (33), and colorectal cancer (34). Overexpression of VEGF has also been reported in OS, and this upregulation is strongly correlated with Enneking stage and distant metastasis (22). OS patients with high VEGF expression levels exhibit an unfavorable prognosis compared with patients with low VEGF levels (23).…”

Section: Discussionmentioning

confidence: 99%

“…3A, the 3'-UTR of VEGF contains a highly conserved binding site for miR-944. Thus, VEGF was selected for investigation to further verify that it serves a crucial role in OS onset and development (22)(23)(24)(25). Subsequently, whether the putative binding site has functional relevance was investigated by luciferase reporter assays.…”

Section: Mir-944 Overexpression Inhibits Os Cell Proliferation and Inmentioning

confidence: 99%

MicroRNA‑944 targets vascular endothelial growth factor to inhibit cell proliferation and invasion in osteosarcoma

Yan

Zhu²,

Zhang

et al. 2018

Mol Med Report

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Emerging evidence has demonstrated that the dysregulation of microRNA (miRNA/miR) serves a crucial role in the tumorigenesis and tumor development of osteosarcoma (OS), primarily by affecting various pathological behaviors. Therefore, better knowledge of miRNA in OS may provide novel insights into the pathogenesis of OS, and may facilitate the development of promising therapeutics for patients with this disease. MiRNA-944 is frequently dysregulated in human cancers. However, the expression levels, functions and underlying mechanisms of miR-944 in OS remain largely elusive. In the present study, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to detect miR-944 expression in OS tissues and cell lines. The regulatory influence of miR-944 in OS proliferation and invasion was determined with MTT and Transwell invasion assays. In addition, the mechanisms underlying the action of miR-944 in OS cells were elucidated through a series of experiments, including bioinformatics analysis, luciferase reporter assay, RT-qPCR and western blot analysis. Spearman's correlation analysis was utilized to examine the relationship between miR-944 and VEGF expression levels, and rescue experiments were applied to further verify whether VEGF mediates the role of miR-944 in OS. The results demonstrated that miR-944 was downregulated in cancer tissues and cell lines. Furthermore, exogenous miR-944 expression inhibited cell proliferation and invasion in OS in vitro. Vascular endothelial growth factor (VEGF) was identified as a direct target of miR-944 in OS and was overexpressed in cancer tissues. VEGF expression was inversely correlated with miR-944 expression in cancer tissues. Rescue experiments demonstrated that overexpression of VEGF partially prevented the miR-944-induced inhibition of OS cell proliferation and invasion. These results suggested that miR-944 may serve a tumor suppressive role in OS by directly targeting VEGF. Therefore, miR-944 may be a promising target in the treatment of OS.

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High expression levels of Cyr61 and VEGF are associated with poor prognosis in osteosarcoma

Cited by 29 publications

References 19 publications

Oncogenic role of sFRP2 in P53-mutant osteosarcoma development via autocrine and paracrine mechanism

Oncogenic role of sFRP2 in P53-mutant osteosarcoma development via autocrine and paracrine mechanism

Oncogenic role of SFRP2 in p53-mutant osteosarcoma development via autocrine and paracrine mechanism

MicroRNA‑944 targets vascular endothelial growth factor to inhibit cell proliferation and invasion in osteosarcoma

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