Metastatic osteosarcoma to the liver and the kidney: a case report and review of the literature

Yu, Wenbin; Yao, Yang

doi:10.1136/bcr.07.2008.0536

“…This result is consistent with the report by Jacques et al [12]. Osteosarcoma is prone to lung metastases [3], and the liver is an extremely rare metastatic site of osteosarcoma [33]. However, in the metastasis mouse models, we found that miR-193a-5p signi cantly enhanced osteosarcoma metastasis to both the lung and liver.…”

Section: Discussionsupporting

confidence: 93%

The MiR-193a-5p/NCX2/AKT Axis Promotes Invasion and Metastasis of Osteosarcoma

Chen

¹

,

Ning

²

,

Zeng³

et al. 2021

Preprint

0

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Background: MiR-193a-5p has been observed to have oncogenic or tumor-suppressive function in different kinds of cancers. Na+/Ca2+ exchangers (NCX1, NCX2 and NCX3) normally extrude Ca2+ from the cell, and deregulation of the intracellular Ca2+ homeostasis is related to several kinds of diseases, including cancer. However, their roles and molecular mechanism in osteosarcoma are elusive.Methods: The expression of miR-193a-5p and NCX2 in osteosarcoma and corresponding adjacent noncancerous tissues was investigated by qRT-PCR. Colony formation assay, wound healing assay, transwell invasion assay and xenograft mouse model were used for in vitro and in vivo functional analyses. Tandem mass tag-based quantitative proteomics analysis was performed to identify the targets of miR-193a-5p.Results: This study showed that miR-193a-5p was upregulated in osteosarcoma tissues compared with the corresponding adjacent noncancerous tissues, and promoted colony formation, migration, invasion, and epithelial-mesenchymal transition (EMT) in vitro, as well as metastasis in vivo. Quantitative proteomics analysis identified NCX2 as a potential target of miR-193a-5p. Luciferase activity assay and Western blotting further confirmed that miR-193a-5p recognized the 3′-untranslated region of NCX2 mRNA, and negatively regulated NCX2 expression. NCX2 was downregulated in osteosarcoma tissues, and its expression was negatively correlated with miR-193a-5p levels. Ectopic expression of NCX2 in osteosarcoma cells could counteract the oncogenic effects of miR-193a-5p. These results indicate that miR-193a-5p exerts its effects by targeting NCX2. Further study demonstrated that NCX2 suppressed Ca2+-dependent Akt phosphorylation by decreasing intracellular Ca2+ efflux, then inhibited EMT process. Treatment with the antagomir against miR-193a-5p sensitized osteosarcoma to the Akt inhibitor afuresertib in a murine xenograft tumor model. Conclusion: This study revealed a miR-193a-5p/NCX2/AKT signaling axis in the progression of osteosarcoma, which may provide a new therapeutic target for osteosarcoma treatment.

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“…This result is consistent with the report by Jacques et al [14]. Osteosarcoma is prone to lung metastases [3], and the liver is an extremely rare metastatic site of osteosarcoma [33]. However, in the metastasis mouse models, we found that miR-193a-5p signi cantly enhanced osteosarcoma metastasis to both the lung and liver.…”

Section: Discussionsupporting

confidence: 93%

The miR-193a-5p/NCX2/AKT axis promotes invasion and metastasis of osteosarcoma

Chen

¹

,

Ning

²

,

Zeng³

et al. 2021

Preprint

0

View full text Add to dashboard Cite

MiR-193a-5p has been observed to have oncogenic or tumor suppressive functions in different kinds of cancers, but its role and molecular mechanism in osteosarcoma are elusive. Na+/Ca2+ exchangers (NCX1, NCX2 and NCX3) normally extrude Ca2+ from the cell, and deregulation of the intracellular Ca2+ homeostasis is related to several kinds of diseases, including cancer. The present study demonstrated that miR-193a-5p was upregulated in osteosarcoma tissues compared with the corresponding adjacent noncancerous tissues, and promoted colony formation, migration, invasion and epithelial-mesenchymal transition (EMT) in osteosarcoma cells (SaOS-2 and U-2OS), as well as metastasis in a murine xenograft model. Tandem mass tag-based quantitative proteomics analysis identified NCX2 as a potential target of miR-193a-5p. Luciferase activity assays and Western blotting further confirmed that miR-193a-5p recognized the 3′-untranslated region of NCX2 mRNA, and negatively regulated NCX2 expression. NCX2 was downregulated in osteosarcoma tissues, and its expression was negatively correlated with miR-193a-5p levels. Ectopic expression of NCX2 in osteosarcoma cells could reverse the oncogenicity of miR-193a-5p, indicating that miR-193a-5p exerted its effects by targeting NCX2. Further study demonstrated that NCX2 suppresses Ca2+-dependent Akt phosphorylation by decreasing intracellular Ca2+ concentration, then inhibited EMT process. Treatment with the antagomir against miR-193a-5p sensitized osteosarcoma to the Akt inhibitor afuresertib in a murine xenograft model. In conclusion, a miR-193a-5p/NCX2/AKT signaling axis contributes to the progression of osteosarcoma, which may provide a new therapeutic target for osteosarcoma treatment.

show abstract

“…Osteosarcoma is prone to lung metastases [3], and the liver is an extremely rare metastatic site of osteosarcoma [33]. However, in the metastasis mouse models, we found that miR-193a-5p signi cantly enhanced osteosarcoma metastasis to both the lung and liver.…”

Section: Discussionmentioning

confidence: 63%

The MiR-193a-5p/NCX2/AKT Axis Promotes Invasion and Metastasis of Osteosarcoma

Chen

¹

,

Ning

²

,

Zeng³

et al. 2021

Preprint

0

View full text Add to dashboard Cite

MiR-193a-5p has been observed to have oncogenic or tumor suppressive functions in different kinds of cancers, but its role and molecular mechanism in osteosarcoma are elusive. Na+/Ca2+ exchangers (NCX1, NCX2 and NCX3) normally extrude Ca2+ from the cell, and deregulation of the intracellular Ca2+ homeostasis is related to several kinds of diseases, including cancer. The present study demonstrated that miR-193a-5p was upregulated in osteosarcoma tissues compared with the corresponding adjacent noncancerous tissues, and promoted colony formation, migration, invasion and epithelial-mesenchymal transition (EMT) in osteosarcoma cells (SaOS-2 and U-2OS), as well as metastasis in a murine xenograft model. Tandem mass tag-based quantitative proteomics analysis identified NCX2 as a potential target of miR-193a-5p. Luciferase activity assays and Western blotting further confirmed that miR-193a-5p recognized the 3′-untranslated region of NCX2 mRNA, and negatively regulated NCX2 expression. NCX2 was downregulated in osteosarcoma tissues, and its expression was negatively correlated with miR-193a-5p levels. Ectopic expression of NCX2 in osteosarcoma cells could reverse the oncogenicity of miR-193a-5p, indicating that miR-193a-5p exerted its effects by targeting NCX2. Further study demonstrated that NCX2 suppresses Ca2+-dependent Akt phosphorylation by decreasing intracellular Ca2+ concentration, then inhibited EMT process. Treatment with the antagomir against miR-193a-5p sensitized osteosarcoma to the Akt inhibitor afuresertib in a murine xenograft model. In conclusion, a miR-193a-5p/NCX2/AKT signaling axis contributes to the progression of osteosarcoma, which may provide a new therapeutic target for osteosarcoma treatment.

show abstract

Metastatic osteosarcoma to the liver and the kidney: a case report and review of the literature

Cited by 9 publications

References 9 publications

The MiR-193a-5p/NCX2/AKT Axis Promotes Invasion and Metastasis of Osteosarcoma

The MiR-193a-5p/NCX2/AKT Axis Promotes Invasion and Metastasis of Osteosarcoma

The miR-193a-5p/NCX2/AKT axis promotes invasion and metastasis of osteosarcoma

The MiR-193a-5p/NCX2/AKT Axis Promotes Invasion and Metastasis of Osteosarcoma

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