Chondrocyte-derived Exosomal miR-195 Inhibits Osteosarcoma Cell Proliferation and Anti-Apoptotic by Targeting KIF4A in vitro and in vivo

AbstractOsteosarcoma is a malignant osteoblastic tumor that can gravely endanger the lives and health of children and adolescents. Therefore, there is an urgent need to explore new biomarkers for osteosarcoma and determine new targeted therapies to improve the efficacy of osteosarcoma treatment. Diaphanous related formin 3 (DIAPH3) promotes tumorigenesis in hepatocellular carcinoma and lung adenocarcinoma, suggesting that DIAPH3 may be a target for tumor therapy. To date, there have been no reports on the function of DIAPH3 in osteosarcoma. DIAPH3 protein expression in osteosarcoma tissues and healthy bone tissues adjacent to cancer cells was examined by immunohistochemical staining. DIAPH3 mRNA expression correlates with overall survival and reduced disease-free survival. DIAPH3 protein is upregulated in osteosarcoma tissues, and its expression is significantly associated with tumor size, tumor stage, node metastasis, and distant metastasis. Functional in vitro experiments revealed that DIAPH3 knockdown suppressed cell proliferation and suppressed cell migration and invasion of osteosarcoma cell lines MG-63 and HOS. Functional experiments demonstrated that DIAPH3 knockdown inhibited subcutaneous tumor growth and lung metastasis in vivo. In conclusion, DIAPH3 expression can predict the clinical outcome of osteosarcoma. In addition, DIAPH3 is involved in the proliferation and metastasis of osteosarcoma, and as such, DIAPH3 may be a potential therapeutic target for osteosarcoma.

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microRNA-194 suppresses osteosarcoma cell proliferation and metastasis in vitro and in vivo by targeting CDH2 and IGF1R

International Journal of Oncology ◽

10.3892/ijo.2014.2571 ◽

2014 ◽

Vol 45 (4) ◽

pp. 1437-1449 ◽

Cited By ~ 48

Author(s):

KANG HAN ◽

TINGBAO ZHAO ◽

XIANG CHEN ◽

NA BIAN ◽

TONGTAO YANG ◽

...

Keyword(s):

Cell Proliferation ◽

Osteosarcoma Cell ◽

Proliferation And Metastasis ◽

Cell Proliferation And Metastasis

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ICT1 Knockdown inhibits osteosarcoma cell proliferation by regulating cell apoptosis through targeting BCL-2

10.21203/rs.3.rs-25599/v1 ◽

2020 ◽

Author(s):

Xiaohui Pan ◽

Jingxue Tan ◽

Rui Du ◽

Yuqing Jiang ◽

Yiping Weng ◽

...

Keyword(s):

Cell Proliferation ◽

Cell Apoptosis ◽

Immunohistochemical Analysis ◽

Osteosarcoma Cell ◽

Inhibitory Effects ◽

Mitochondrial Translation ◽

Functional Studies ◽

Translation Methods

Abstract Background Osteosarcoma (OS) which occurs mainly in the young people is a common malignant bone tumor. Apoptosis is a form of programmed and controlled cell death and promoting apoptosis of OS cells is an important treatment for OS. However, the pathways of controlling apoptosis in OS remain unclear. Immature colon carcinoma transcript-1 (ICT1) which is previously named DS-1 belongs to a family of four putative mitochondrial translation release factors. It controls the termination stage of translation. Methods In this study, the function of ICT1 was elucidated by a series of in vivo and in vitro assays. The potential downstream targets of ICT1 in the OS was identified by qRT-PCR and western blotting, while immunohistochemical analysis and rescue experiment were performed to confirm this result. Results ICT1 was upregulated in OS, and higher expression of ICT1 was associated with worse overall survival rate. Functional studies suggested that knockdown of ICT1 could inhibit OS cell proliferation in vitro or in vivo. In addition, suppression of ICT1 could promote apoptosis of OS cells. Furthermore, we demonstrated that BCL-2, apoptotic related-genes, is a potential target of ICT1 and BCL-2 overexpression partly reversed the inhibitory effects of ICT1 knockdown on the pro-tumorigenic properties of OS cells in vitro. Conclusion The ICT1 protein was overexpressed in the OS and has identified a novel mechanism by which ICT1 inhibits osteosarcoma cell proliferation by regulating cell apoptosis through targeting BCL-2.

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ICG-001, an Inhibitor of the β-Catenin and cAMP Response Element-Binding Protein Dependent Gene Transcription, Decreases Proliferation but Enhances Migration of Osteosarcoma Cells

Pharmaceuticals ◽

10.3390/ph14050421 ◽

2021 ◽

Vol 14 (5) ◽

pp. 421

Author(s):

Geoffroy Danieau ◽

Sarah Morice ◽

Sarah Renault ◽

Régis Brion ◽

Kevin Biteau ◽

...

Keyword(s):

Cell Proliferation ◽

Mouse Model ◽

Cell Lines ◽

Gene Transcription ◽

Pediatric Population ◽

Wnt Signaling Pathway ◽

Osteosarcoma Cell ◽

Metastatic Dissemination

High-grade osteosarcomas are the most frequent malignant bone tumors in the pediatric population, with 150 patients diagnosed every year in France. Osteosarcomas are associated with low survival rates for high risk patients (metastatic and relapsed diseases). Knowing that the canonical Wnt signaling pathway (Wnt/β-catenin) plays a complex but a key role in primary and metastatic development of osteosarcoma, the aim of this work was to analyze the effects of ICG-001, a CBP/β-catenin inhibitor blocking the β-catenin dependent gene transcription, in three human osteosarcoma cell lines (KHOS, MG63 and 143B). The cell proliferation and migration were first evaluated in vitro after ICG-001 treatment. Secondly, a mouse model of osteosarcoma was used to establish the in vivo biological effect of ICG-001 on osteosarcoma growth and metastatic dissemination. In vitro, ICG-001 treatment strongly inhibits osteosarcoma cell proliferation through a cell cycle blockade in the G0/G1 phase, but surprisingly, increases cell migration of the three cell lines. Moreover, ICG-001 does not modulate tumor growth in the osteosarcoma mouse model but, rather significantly increases the metastatic dissemination to lungs. Taken together, these results highlight, despite an anti-proliferative effect, a deleterious pro-migratory role of ICG-001 in osteosarcoma.

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LncRNA RBM5-AS1 Promotes Osteosarcoma Cell Proliferation, Migration, and Invasion

BioMed Research International ◽

10.1155/2021/5271291 ◽

2021 ◽

Vol 2021 ◽

pp. 1-9

Author(s):

Biyong Deng ◽

Runsang Pan ◽

Xin Ou ◽

Taizhe Wang ◽

Weiguo Wang ◽

...

Keyword(s):

Cell Proliferation ◽

Cell Lines ◽

Western Blotting ◽

Migration And Invasion ◽

Osteosarcoma Cell ◽

Pediatric Age Group ◽

The Relationship

Purpose. Osteosarcoma (Os) is the most frequent malignant tumor of the bone in the pediatric age group, and accumulating evidences show that lncRNAs play a key role in the development of Os. Thus, we investigated the role of RBM5-AS1 and its molecular mechanism. Methods. The expression of RBM5-AS1 in Os tissues and cell lines was detected by real-time polymerase chain reaction (QPCR). The effect of RBM5-AS1 on the proliferation of Os cells was detected using CCK8 assays and flow cytometry. The effect of RBM5-AS1 on the migration and invasion of Os cells was detected by transwell assays. And we performed QPCR and western blotting assays to investigate the relationship between RBM5-AS1 and RBM5. Finally, western blotting assays were performed to explore the mechanism of RBM5. Results. LncRNA RBM5-AS1 was overexpressed in the Os tissues and cell lines. And lncRNA RBM5-AS1 promoted Os cell proliferation, migration, and invasion in vitro and tumor growth in vivo. LncRNA RBM5-AS1 targets RBM5 in Os cells. Conclusion. To sum up, the results showed that lncRNA RBM5-AS1 promotes cell proliferation, migration, and invasion in Os.

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Downregulation of UBE2T can enhance the radiosensitivity of osteosarcoma in vitro and in vivo

Epigenomics ◽

10.2217/epi-2019-0125 ◽

2019 ◽

Vol 11 (11) ◽

pp. 1283-1305

Author(s):

Lin Shen ◽

Kai Zhao ◽

Han Li ◽

Bin Ning ◽

Wenzhao Wang ◽

...

Keyword(s):

Cell Cycle ◽

Cell Proliferation ◽

Immunohistochemical Analysis ◽

Gene Expression Omnibus ◽

Osteosarcoma Cell ◽

M Phase ◽

And Migration ◽

Species Production

Aim: To investigate the effect of UBE2T gene on radiotherapy for osteosarcoma. Materials & methods: Gene Expression Omnibus database, RT-qPCR and immunohistochemical analysis were performed. Cell proliferation and cell cycle experiments were conducted after knockdown of UBE2T. Cell scratch, reactive oxygen species production and apoptosis experiments were conducted after the combination of radiotherapy and UBE2T silencing. Then the xenograft mode was further conducted. Results: UBE2T was highly expressed in human osteosarcoma. Suppression of UBE2T inhibited osteosarcoma cell proliferation and induced cell cycle arrest at the G2/M phase. Downregulation of UBE2T combined with radiation can substantially inhibit clonal formation and migration, and promote apoptosis of osteosarcoma cells in vitro and in vivo. Conclusion: UBE2T downregulation can enhance the radiosensitivity of osteosarcoma in vitro and in vivo.

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Cullin-1 Regulates MG63 Cell Proliferation and Metastasis and is a Novel Prognostic Marker of Osteosarcoma

The International Journal of Biological Markers ◽

10.5301/jbm.5000247 ◽

2017 ◽

Vol 32 (2) ◽

pp. 202-209 ◽

Cited By ~ 3

Author(s):

Qinghua Cheng ◽

Guoyong Yin

Keyword(s):

Cell Proliferation ◽

Mg63 Cell ◽

Osteosarcoma Cell ◽

Mmp9 Expression ◽

Proliferation And Metastasis ◽

Reliable Marker ◽

Proliferation In Vitro

Background There is no reliable marker available for early detection, diagnostic confirmation or disease prognosis of osteosarcoma. Cullin-1 (CUL1) is a newly reported tumor-related gene, and we aimed to unravel its role in osteosarcoma. Methods We used immunohistochemistry to analyze the correlation between CUL1 expression and clinicopathological variables and patient survival. To evaluate the function of CUL1, a group of 28 osteosarcoma patients were recruited for this study. The role of regulation of CUL1 in osteosarcoma was studied in vitro and in vivo. In addition, we further investigated the signaling pathway of CUL1 in osteosarcoma progression. Results We first discovered that CUL1 expression was up-regulated in human osteosarcoma tissues and inversely correlated with osteosarcoma differentiation. In addition, CUL1 promotes osteosarcoma cell proliferation in vitro and in vivo. We also found that CUL1 promotes osteosarcoma cell invasion and metastasis in vitro and in vivo. High levels of CUL1 promote osteosarcoma progression via up-regulation of MMP9 expression. Conclusions Our results demonstrate that increased CUL1 expression is significantly correlated with poor prognosis of patients with osteosarcoma. CUL1 might be an important marker and a therapeutic target for osteosarcoma.

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Knockdown of MCM8 functions as a strategy to inhibit the development and progression of osteosarcoma through regulating CTGF

Cell Death and Disease ◽

10.1038/s41419-021-03621-y ◽

2021 ◽

Vol 12 (4) ◽

Author(s):

Zhinan Ren ◽

Jun Li ◽

Shanwen Zhao ◽

Qi Qiao ◽

Runguang Li

Keyword(s):

Cell Proliferation ◽

Tumor Grade ◽

Mechanistic Study ◽

Osteosarcoma Cell ◽

Downstream Target ◽

Normal Tissues ◽

Advanced Tumor ◽

Regulatory Effects

AbstractOsteosarcoma is the most common primary malignant tumor of bone derived from osteoblasts, which is a noteworthy threat to the health of children and adolescents. In this study, we found that MCM8 has significantly higher expression level in osteosarcoma tissues in comparison with normal tissues, which was also correlated with more advanced tumor grade and pathological stage. In agreement with the role of MCM proteins as indicators of cell proliferation, knockdown/overexpression of MCM8 inhibited/promoted osteosarcoma cell proliferation in vitro and tumor growth in vivo. Also, MCM8 knockdown/overexpression was also significantly associated with the promotion/inhibition of cell apoptosis and suppression/promotion of cell migration. More importantly, mechanistic study identified CTGF as a potential downstream target of MCM8, silencing of which could enhance the regulatory effects of MCM8 knockdown and alleviate the effects of MCM8 overexpression on osteosarcoma development. In summary, MCM8/CTGF axis was revealed as critical participant in the development and progression of osteosarcoma and MCM8 may be a promising therapeutic target for osteosarcoma treatment.

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MicroRNA-24 inhibits osteosarcoma cell proliferation both in vitro and in vivo by targeting LPAATβ

Archives of Biochemistry and Biophysics ◽

10.1016/j.abb.2013.04.001 ◽

2013 ◽

Vol 535 (2) ◽

pp. 128-135 ◽

Cited By ~ 41

Author(s):

Lei Song ◽

Jie Yang ◽

Ping Duan ◽

Jianzhong Xu ◽

Xiangdong Luo ◽

...

Keyword(s):

Cell Proliferation ◽

Osteosarcoma Cell

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ICT1 Knockdown inhibits osteosarcoma cell proliferation by regulating cell apoptosis through targeting BCL-2

10.21203/rs.3.rs-25599/v2 ◽

2020 ◽

Author(s):

Xiaohui Pan ◽

Jingxue Tan ◽

Rui Du ◽

Yuqing Jiang ◽

Yiping Weng ◽

...

Keyword(s):

Cell Proliferation ◽

Cell Apoptosis ◽

Immunohistochemical Analysis ◽

Negative Influence ◽

Osteosarcoma Cell ◽

Mitochondrial Translation ◽

Rescue Experiment ◽

Polymerase Chain

Abstract Background:Osteosarcoma (OS) which occurs mainly in the young people is a familiar malignant bone tumor. Apoptosis is a kind of programmed and managed cell death and promoting apoptosis of OS cells is an important treatment for OS. However, the pathways of controlling apoptosis in OS remain unclear. Immature colon carcinoma transcript-1 (ICT1) belongs to a family of four putative mitochondrial translation release factors. It controls the termination stage of translation. Methods:In this study, the function of ICT1 was elucidated by a series of in vivo and in vitro assays. The potential downstream targets of ICT1 in the OS was confirmed by Quantitative real‑time polymerase chain reaction (qRT-PCR) and western blotting, while immunohistochemical analysis and rescue experiment were performed to confirm this result. Results: ICT1 was significantly upregulated in osteosarcoma, and higher expression of ICT1 led to the worse survival rate. Furthermore, knockdown of ICT1 could inhibit the cell proliferation, but improved the apoptosis of cells in vitro and in vivo. In addition, our data demonstrated that BCL-2, apoptotic related-genes, is a potential target of ICT1 and the overexpression of BCL-2 partly reduced the negative influence of ICT1 knockdown on the pro-tumorigenic capabilities of OS cells in vitro. Conclusion: The ICT1 protein was overexpressed in the OS and has identified a novel mechanism by which ICT1 inhibits osteosarcoma cell proliferation by regulating cell apoptosis through targeting BCL-2.

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