The microRNA‑708‑5p/ZEB1/EMT axis mediates the metastatic potential of osteosarcoma

Feng, Tianyu; Zhu, Zhongkai; Jin, Yinlong; Wang, Hao; Mao, Xiaohan; Liu, Dan; Li, Yiling; Lu, Lixia; Zuo, Guo‐Wei

doi:10.3892/or.2019.7452

Cited by 17 publications

(17 citation statements)

References 40 publications

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“…Invasion, metastasis, immune evasion, and drug resistance would increase when tumor cells undergo EMT (33,34). Studies revealed that EMT in OS could promoted tumor growth and metastasis (35)(36)(37)(38). In our studies, we found that downregulation of Siglec-15 could not only reduce the Matrix metalloproteinases are zinc (Zn 2+ ) dependent endopeptidases which cause degradation of extracellular matrix proteins such as collagen, laminin, and fibronectin and further lead to the extracellular matrix remodeling (39).…”

Section: Discussionmentioning

confidence: 70%

Siglec-15 Promotes Tumor Progression in Osteosarcoma via DUSP1/MAPK Pathway

et al. 2021

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Recurrence and metastasis are important features of osteosarcoma (OS) that cause its poor prognosis. Aberrant expression of Sialic acid-binding immunoglobulin-like lectin 15 (Siglec-15) has been reported in various kinds of cancers. However, the expression and function of Siglec-15 in OS remain unclear. In cultured OS cells (143B cells and MNNG/HOS cells) and their xenograft mouse models, we found that downregulation of Siglec-15 could inhibit the proliferation, migration and invasion of by inducing epithelial-mesenchymal transition (EMT) in vitro and in vivo. Conversely, Siglec-15 overexpression promoted the growth, migration and invasion of OS cells in a significant manner. Then, we screened a number of differentially expressed genes (DEGs) between Siglec-15-knockdown group and control group by RNA-Seq assay. Among these DEGs, we found that dual-specificity phosphatase 1 (DUSP1/MKP1) was significantly downregulated after Siglec-15 silencing. We investigated the DUSP1 functions in influencing OS cells’ biology, and found that the proliferation, migration and invasion of OS cells were promoted by overexpressing DUSP1 and crucially, the proliferation, migration and invasion of Siglec-15-knockdown OS cells were rescued by overexpressing DUSP1. Mechanically, we further showed that DUSP1-mediated inhibition of p38/MAPK and JNK/MAPK expression was attenuated when Siglec-15 expression was inhibited, suggesting that Siglec-15 promotes the malignant progression of OS cells by suppressing DUSP1-mediated suppression of the MAPK pathway. Moreover, we showed that both Siglec-15 and DUSP1 were highly expressed in human OS tissues by immunohistochemistry. High Siglec-15 expression was associated with OS lung metastasis, and high DUSP1 expression was associated with the high Enneking stage. Kaplan–Meier analysis indicated that high expression of Siglec-15 could predict poor prognosis of OS patients. Altogether, these results showed that Siglec-15 expression promoted OS development and progression by activating DUSP1 and might be a novel target in OS treatment.

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Section: Discussionmentioning

confidence: 70%

Siglec-15 Promotes Tumor Progression in Osteosarcoma via DUSP1/MAPK Pathway

et al. 2021

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“…For example, miR-708-5p, miR-126, and miR-130a impair osteosarcoma EMT, migration, invasion, and metastasis by directly inhibiting ZEB1 expression and miR-708-5p also downregulates MMP-2, MMP-7 and MMP-9. [103][104][105] In a similar manner, overexpression of miR-30d repressed EwS cell migration and invasion by inhibiting PI3K/AKT/mTOR and MAPK/ ERK pathways as well as MMP-2 and MMP-9 levels. 106 Recently, miR-200b-3p, miR-30c-1-3P, and miR-363-3P were reported to inhibit GIST invasion via direct downregulation of SNAI2.…”

Section: Alterations In Cell Cycle Regulatorsmentioning

confidence: 80%

Molecular mechanisms underpinning sarcomas and implications for current and future therapy

Damerell

Pepper

Prince

2021

Sig Transduct Target Ther

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Sarcomas are complex mesenchymal neoplasms with a poor prognosis. Their clinical management is highly challenging due to their heterogeneity and insensitivity to current treatments. Although there have been advances in understanding specific genomic alterations and genetic mutations driving sarcomagenesis, the underlying molecular mechanisms, which are likely to be unique for each sarcoma subtype, are not fully understood. This is in part due to a lack of consensus on the cells of origin, but there is now mounting evidence that they originate from mesenchymal stromal/stem cells (MSCs). To identify novel treatment strategies for sarcomas, research in recent years has adopted a mechanism-based search for molecular markers for targeted therapy which has included recapitulating sarcomagenesis using in vitro and in vivo MSC models. This review provides a comprehensive up to date overview of the molecular mechanisms that underpin sarcomagenesis, the contribution of MSCs to modelling sarcomagenesis in vivo, as well as novel topics such as the role of epithelial-to-mesenchymal-transition (EMT)/mesenchymal-to-epithelial-transition (MET) plasticity, exosomes, and microRNAs in sarcomagenesis. It also reviews current therapeutic options including ongoing pre-clinical and clinical studies for targeted sarcoma therapy and discusses new therapeutic avenues such as targeting recently identified molecular pathways and key transcription factors.

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“…Previous study displayed miR-708-5p overexpression repressed cell viability and migration, and promoted cell apoptosis in osteosarcoma ( Sui et al, 2019 ). Feng et al (2020) also investigated that miR-708-5p hindered cell migration and invasion in osteosarcoma. Similarly, in our view, miR-708-5p inhibitor attenuated the inhibition effects of Sch B on cell viability and migration, and the promotion effect of Sch B on cell apoptosis, which suggested that miR-708-5p hindered cell viability and migration, but induced cell apoptosis in osteosarcoma.…”

Section: Discussionmentioning

confidence: 99%

Schisandrin B Inhibits Cell Viability and Migration, and Induces Cell Apoptosis by circ_0009112/miR-708-5p Axis Through PI3K/AKT Pathway in Osteosarcoma

Wang

Xing

et al. 2020

Front. Genet.

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Osteosarcoma is a primary tumor of bone and its incidence is increasing. Schisandrin B (Sch B), a generally used lignan in Chinese medicine, has been found to repress cancer progression. This study aims to reveal the effects and regulatory mechanism of Sch B in the viability, apoptosis and migration of osteosarcoma cells. In this study, we found circ_0009112 expression was higher and miR-708-5p expression was lower in SaOS2 and U2OS cells than in hFOB1.19 cells. Circ_0009112 expression was downregulated, but miR-708-5p was upregulated by Sch B treatment in a dose-dependent manner in SaOS2 and U2OS cells. Sch B exposure inhibited osteosarcoma development in vitro and in vivo; however, these effects were restored by circ_0009112. Furthermore, circ_0009112 acted as a sponge of miR-708-5p. Circ_0009112 regulated PI3K/AKT pathway after Sch B treatment by associating with miR-708-5p. Sch B exposure inhibited cell viability and migration, whereas promoted cell apoptosis by regulating circ_0009112/miR-708-5p axis through PI3K/AKT pathway in osteosarcoma cells. This study provided a theoretical basis for further studying osteosarcoma therapy with Sch B.

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The microRNA‑708‑5p/ZEB1/EMT axis mediates the metastatic potential of osteosarcoma

Cited by 17 publications

References 40 publications

Siglec-15 Promotes Tumor Progression in Osteosarcoma via DUSP1/MAPK Pathway

Siglec-15 Promotes Tumor Progression in Osteosarcoma via DUSP1/MAPK Pathway

Molecular mechanisms underpinning sarcomas and implications for current and future therapy

Schisandrin B Inhibits Cell Viability and Migration, and Induces Cell Apoptosis by circ_0009112/miR-708-5p Axis Through PI3K/AKT Pathway in Osteosarcoma

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