scholarly journals WIN55,212-2-Induced Expression of Mir-29b1 Favours the Suppression of Osteosarcoma Cell Migration in a SPARC-Independent Manner

2019 ◽  
Vol 20 (20) ◽  
pp. 5235 ◽  
Author(s):  
Antonietta Notaro ◽  
Sonia Emanuele ◽  
Fabiana Geraci ◽  
Antonella D’Anneo ◽  
Marianna Lauricella ◽  
...  
Keyword(s):  
Cell Migration ◽  
Extracellular Vesicles ◽  
Cannabinoid Receptors ◽  
Matricellular Protein ◽  
Osteosarcoma Cell ◽  
Osteosarcoma Cells ◽  
Independent Manner ◽  
Matrix Deposition ◽  
Extracellular Matrix Deposition ◽  
And Migration

WIN55,212-2 (WIN) is a synthetic agonist of cannabinoid receptors that displays promising antitumour properties. The aim of this study is to demonstrate that WIN is able to block the migratory ability of osteosarcoma cells and characterize the mechanisms involved. Using wound healing assay and zymography, we showed that WIN affects cell migration and reduces the activity of the metalloproteases MMP2 and MMP9. This effect seemed to be independent of secreted protein acidic and rich in cysteine (SPARC), a matricellular protein involved in tissue remodeling and extracellular matrix deposition. SPARC release was indeed prevented by WIN, and SPARC silencing by RNA interference did not influence the effect of the cannabinoid on cell migration. WIN also increased the release of extracellular vesicles and dramatically upregulated miR-29b1, a key miRNA that modulates cell proliferation and migration. Interestingly, reduced cell migration was observed in stably miR-29b1-transfected cells, similarly to WIN-treated cells. Finally, we show the absence of SPARC in the extracellular vesicles released by osteosarcoma cells and no changes in SPARC level in miR-29b1 overexpressing cells. Overall, these findings suggest that WIN markedly affects cell migration, dependently on miR-29b1 and independently of SPARC, and can thus be considered as a potential innovative therapeutic agent in the treatment of osteosarcoma.

scholarly journals Exosomal miR-1228 From Cancer-Associated Fibroblasts Promotes Cell Migration and Invasion of Osteosarcoma by Directly Targeting SCAI

2019 ◽  
Vol 27 (9) ◽  
pp. 979-986 ◽  
Author(s):  
Jian-Wei Wang ◽  
Xiao-Feng Wu ◽  
Xiao-Juan Gu ◽  
Xing-Hua Jiang
Keyword(s):  
Cell Migration ◽  
Migration And Invasion ◽  
Osteosarcoma Cell ◽  
Cancer Associated Fibroblasts ◽  
Osteosarcoma Cells ◽  
Mirna Microarray ◽  
Cell Migration And Invasion ◽  
Invasion And Migration ◽  
And Migration

Cancer-associated fibroblasts (CAFs) play a predominant role in regulating tumor progression. Understanding how CAFs communicate with osteosarcoma is crucial for developing novel approaches for osteosarcoma therapy. Exosomes are able to transmit messages between cells. In this study, we demonstrated that CAFs transfer exosomes to osteosarcoma cells, which promotes osteosarcoma cell migration and invasion. Using a miRNA microarray analysis, we identified 13 miRNAs that are significantly increased in exosomes derived from cancer-associated fibroblasts (CAFs) and corresponding paracancer fibroblasts (PAFs). In vitro studies further validated that the levels of microRNA-1228 (miR-1228) were increased in CAFs, its secreted exosomes, and in recipient osteosarcoma cells, which can downregulate endogenous SCAI mRNA and protein level in osteosarcoma. Furthermore, our findings demonstrate that SCAI was downregulated in osteosarcoma tissues. Taken together, this study provides evidence that CAF exosomal miR-1228 is able to promote osteosarcoma invasion and migration by targeting SCAI, which may represent a critical therapeutic target for osteosarcoma treatment.

scholarly journals Circ-FOXM1 Promotes Cell Proliferation, Migration and EMT Process in Osteosarcoma Through FOXM1-Mediated Wnt Pathway Activation

2021 ◽  
Author(s):  
Hao Zhang ◽  
Qiongqiong Zhou
Keyword(s):  
Cell Proliferation ◽  
Cell Migration ◽  
Cell Apoptosis ◽  
Biological Activities ◽  
Wnt Signaling Pathway ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Transcriptional Level ◽  
Osteosarcoma Cell ◽  
Osteosarcoma Cells

Abstract Background: As the most common primary bone tumor in adolescents and children, osteosarcoma commonly occurs with high mortality rate and metastasis. Emerging evidence has illustrated that circular RNAs (circRNAs) are important regulatory RNAs that are involved in multiple biological activities of carcinomas. Circ-FOXM1 (hsa_circ_0025033) is a recently found circRNA and promotes the cellular activities of several cancers. However, the function and molecular mechanism of circ-FOXM1 in osteosarcoma have not been interrogated yet. Methods: The qRT-PCR was utilized to test the expression of circ-FOXM1 in osteosarcoma cell lines. Loss-of-function assays including CCK-8, EdU, TUNEL, transwell and western blot assays were conducted to measure cell proliferation, cell migration, EMT process and cell apoptosis. Luciferase reporter assay and RIP assay were utilized to detect the interaction of circ-FOXM1 and RNAs. Results：We discovered the high expression of circ-FOXM1 in osteosarcoma cells. Besides, it was indicated that circ-FOXM1 knockdown inhibited cell proliferation, cell migration and EMT process, as well as induced cell apoptosis of osteosarcoma cells. Furthermore, circ-FOXM1 was discovered to upregulate the expression level of forkhead box M1 (FOXM1) at post-transcriptional level. Moreover, it was proved that circ-FOXM1 sponged miR-320a and miR-320b so as to increase FOXM1 expression. Additionally, circ-FOXM1 could activate Wnt signaling pathway through upregulating FOXM1. In the end, rescue assays certified that FOXM1 overexpression could totally rescue the circ-FOXM1 silence-repressed cellular activities of osteosarcoma cells.Conclusion: Circ-FOXM1 facilitated the progression of osteosarcoma cells via relieving FOXM1 from the inhibition by miR-320a and miR-320b.

scholarly journals Degradation of long non-coding RNA-CIR decelerates proliferation, invasion and migration, but promotes apoptosis of osteosarcoma cells

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Shiwei Liu ◽  
Jingchao Li ◽  
Liang Kang ◽  
Yueyang Tian ◽  
Yuan Xue
Keyword(s):  
Tumor Growth ◽  
Osteosarcoma Cell ◽  
Loss Of Function ◽  
Osteosarcoma Cells ◽  
Invasion And Migration ◽  
Normal Tissues ◽  
Novel Target ◽  
And Migration

Abstract Background Over the years, long non-coding RNAs (lncRNAs) have been clarified in malignancies, this research was focused on the role of lncRNA cartilage injury-related (lncRNA-CIR) in osteosarcoma cells. Methods LncRNA-CIR expression in osteosarcoma tissues and cells, and adjacent normal tissues and normal osteoblasts was determined, then the relations between lncRNA-CIR expression and the clinicopathological features, and between lncRNA-CIR expression and the prognosis of osteosarcoma patients were analyzed. Moreover, the MG63 and 143B cells were treated with silenced or overexpressed lncRNA-CIR, and then the proliferation, invasion, migration and apoptosis of the cells were evaluated by gain- and loss-of-function approaches. The tumor growth, and proliferation and apoptosis of osteosarcoma cells in vivo were observed by subcutaneous tumorigenesis in nude mice. Results We have found that lncRNA-CIR was up-regulated in osteosarcoma tissues and cells, which was respectively relative to adjacent normal tissues and normal osteoblasts. The expression of lncRNA-CIR was evidently correlated with disease stages, distant metastasis and differentiation of osteosarcoma patients, and the high expression of lncRNA-CIR indicated a poor prognosis. Furthermore, the reduction of lncRNA-CIR could restrict proliferation, invasion and migration, but promote apoptosis of osteosarcoma cells in vitro. Meanwhile, inhibited lncRNA-CIR also restrained tumor growth and osteosarcoma cell proliferation, whereas accelerated apoptosis of osteosarcoma cells in vivo. Conclusion We have found in this study that the inhibited lncRNA-CIR could decelerate proliferation, invasion and migration, but accelerate apoptosis of osteosarcoma cells, which may provide a novel target for osteosarcoma treatment.

scholarly journals Interfering with pak4 Protein Expression Affects Osteosarcoma Cell Proliferation and Migration

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Yuxin Fu ◽  
Lun Fang ◽  
Qipu Yin ◽  
Qi Wu ◽  
Wei Sui ◽  
...  
Keyword(s):  
Protein Expression ◽  
Osteosarcoma Cell ◽  
Mrna Levels ◽  
Osteosarcoma Cells ◽  
Migration Ability ◽  
M Phase ◽  
Underlying Mechanisms ◽  
And Migration ◽  
Proliferation And Migration

Purpose. A number of studies have discovered various roles of PAK4 in human tumors, including osteosarcoma. However, the exact role of PAK4 in osteosarcoma and its mechanism have yet to be determined. Therefore, this study focused on interrogating the PAK4 effect on the proliferation and migration ability of osteosarcoma and its underlying mechanisms. Materials and Methods. Western blot and QRT-PCR were utilized to quantify the PAK4 relative protein and mRNA levels. To measure cellular viability and mobility, the MTT and wound-healing assays were preferred. Results. With the adenovirus-mediated overexpression of PAK4, the proliferation and migration of U2-OS and MG-63 osteosarcoma cells were stimulated. Furthermore, a liposome-mediated knockout of PAK4 will inhibit osteosarcoma cells from proliferating. In terms of mechanism, we observed the positive correlation of PAK4 expression with expression of P21, CyclinD1, CyclinE1, CDK2, and CDK6, which drives G0/G1 to the G2/M phase transition. PAK4 can also activate Erk expression in OS cells and induce EMT. Conclusion. Interfering with PAK4 protein expression has been shown to affect osteosarcoma proliferation and migration.

Using Bioinformatics Analysis to Detect the Effect of Zoledronic Acid on the Biological Behavior of Osteosarcoma Cells

2019 ◽  
Vol 9 (8) ◽  
pp. 1568-1574
Author(s):  
Sheng Li ◽  
Jianjun Li
Keyword(s):  
Cell Proliferation ◽  
Zoledronic Acid ◽  
Side Effects ◽  
Bioinformatics Analysis ◽  
Biological Behavior ◽  
Osteosarcoma Cell ◽  
Osteosarcoma Cells ◽  
Migration Ability ◽  
And Migration ◽  
Proliferation And Migration

Objective: Osteosarcoma is a malignant bone tumor commonly seen in adolescents. Drug treatment for osteosarcoma is often accompanied by systemic toxicity and side effects, while zoledronic acid has few side effects but has anti-tumor effects. Methods: The bioinformatics analysis and scratch test were used to detect changes in cell proliferation, migration, and apoptosis in two osteosarcoma cell lines 24, 48, and 72 hours after adding zoledronic acid (0, 25, 50, 100, and 200 μM). Flow cytometry and transmission electron microscopy were used to observe the changes in cell apoptosis in the control and experimental groups after a 50% inhibitory dose of zoledronic acid was given. Results: The inhibition of cell proliferation and migration ability, as well as apoptosis increased with the increase in zoledronic acid exposure time and concentration. The 50% inhibitory rate occurred 48 hours after treatment with 100 M zoledronic acid. Conclusion: Zoledronic acid inhibited proliferation and migration and promoted apoptosis of osteosarcoma cells in vitro.

scholarly journals Lipocalin-2 Inhibits Osteosarcoma Cell Metastasis by Suppressing MET Expression via the MEK–ERK Pathway

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3181
Author(s):  
Ko-Hsiu Lu ◽  
Jia-Sin Yang ◽  
Yi-Hsien Hsieh ◽  
Hsiao-Ju Chu ◽  
Chia-Hsuan Chou ◽  
...  
Keyword(s):  
Cellular Migration ◽  
Migration And Invasion ◽  
Osteosarcoma Cell ◽  
Erk Pathway ◽  
Lipocalin 2 ◽  
Cellular Motility ◽  
Osteosarcoma Cells ◽  
Cell Metastasis ◽  
Mitogen Activated Protein ◽  
And Migration

Higher neutrophil-derived cytokine lipocalin-2 (LCN2) expression possesses a versatile role in a myriad of cancers, but little is known about the role of LCN2 on osteosarcoma metastasis. In this study, we demonstrated that higher LCN2 inhibited cellular motility, migration, and invasion of osteosarcoma cells. Moreover, using RNA sequencing technology, we found that LCN2 repressed MET gene expression in U2OS cells. Manipulation of LCN2 levels influenced the migratory potential of osteosarcoma cells as cellular migration was enhanced by transfecting with vectors containing a constitutively active LCN2 cDNA and recombinant human LCN2. Moreover, the phosphorylation of mitogen-activated protein kinases/extracellular signal-regulated kinase (ERK) kinase (MEK) 1/2 and ERK 1/2 was decreased by LCN2 knockdown. Furthermore, the use of ERK inhibitor (U0126) and activator (tBHQ) confirmed that the pharmaceutic inhibition of MEK–ERK augmented the LCN2-mediated MET suppression and migration of U2OS and HOS cells. Conclusively, LCN2 inhibits osteosarcoma cell metastasis by suppressing MET via the MEK–ERK pathway.

scholarly journals miR-194 Suppresses Proliferation and Migration and Promotes Apoptosis of Osteosarcoma Cells by Targeting CDH2

2018 ◽  
Vol 45 (5) ◽  
pp. 1966-1974 ◽  
Author(s):  
Jinglei Miao ◽  
Weiguo Wang ◽  
Song Wu ◽  
Xiaofang Zang ◽  
Yuezhan Li ◽  
...  
Keyword(s):  
Tumour Suppressor ◽  
Osteosarcoma Cell ◽  
Osteosarcoma Cells ◽  
Migration Assay ◽  
Tumour Suppression ◽  
Normal Bone ◽  
Proliferation Ability ◽  
And Migration ◽  
Normal Bone Tissue ◽  
Proliferation And Migration

Background/Aims: Studies have shown that miR-194 functions as a tumour suppressor and is associated with tumour growth and metastasis. This study intends to uncover the mechanism of tumour suppression by miR-194. The expression of miR-194 in osteosarcoma cell lines and tissues were monitored by real-time PCR. Methods: The proliferation ability was examined by MTT assay. Migration and apoptosis of cells were monitored by migration assay and flow cytometry, respectively. The regulation of miR-194 on CDH2 was determined by luciferase assays and western blot assays. Results: The results showed that miR-194 was significantly reduced in osteosarcoma compared with that in normal bone tissue. Overexpression of miR-194 significantly attenuated the proliferation and migration and induced the apoptosis of osteosarcoma cells. Furthermore, we demonstrated that miR-194 has inhibited the malignant behaviour of osteosarcoma by downregulating CDH2 expression. Conclusions: These findings suggested that miR-194 may act as a tumour suppressor in osteosarcoma. miR-194/CDH2 may be a novel therapeutic target in the treatment of osteosarcoma.

Knockdown of Kinesin Family 15 Inhibits Osteosarcoma through Suppressing Cell Proliferation and Promoting Cell Apoptosis

Chemotherapy ◽  
2019 ◽  
Vol 64 (4) ◽  
pp. 187-196
Author(s):  
Zhiqiang Wu ◽  
Hao Zhang ◽  
Zhengwang Sun ◽  
Chunmeng Wang ◽  
Yong Chen ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Apoptosis ◽  
Flow Cytometric Analysis ◽  
Osteosarcoma Cell ◽  
Osteosarcoma Cells ◽  
Expression Levels ◽  
Invasion And Migration ◽  
Normal Tissues ◽  
And Migration ◽  
Kinesin Family

Kinesin family (KIF) members have vital roles in mitosis, meiosis, and transport of macromolecules in eukaryotic cells. In this study, we aimed to investigate the role of KIF15 in osteosarcoma. Immunohistochemical staining was performed to determine expression levels of KIF15 in osteosarcoma tissues and adjacent normal tissues. Tissue microarray analysis showed a correlation between the expression of KIF15 and pathological features of patients. Subsequently, lentivirus was used to inhibit the expression of KIF15 in osteosarcoma cells. An MTT assay was performed to examine cell proliferation. Transwell and wound healing assays were used to estimate the invasion and migration of osteosarcoma cells, respectively. Flow cytometric analysis was employed to define the apoptosis of osteosarcoma cells. Our results showed that KIF15 expression was significantly upregulated in osteosarcoma tissues compared with adjacent normal tissues. The Mann-Whitney U test and Spearman correlation analysis showed that the expression levels of KIF15 in osteosarcoma tissues were positively correlated with tumor infiltrate, a pathological characteristic of patients. The expression of KIF15 was successfully suppressed by shKIF15, and the knockdown efficiency reached 80 and 69% in MNNG/HOS and U2OS cells, respectively. Subsequently, knockdown of KIF15 significantly inhibited the capacity of cell proliferation, colony formation, invasion, and migration, but enhanced G2 phase arrest and partially enhanced cell apoptosis. This study preliminarily showed KIF15 to be a critical regulatory molecule involved in osteosarcoma cell proliferation. Consequently, KIF15 can be a potential diagnostic and therapeutic target for osteosarcoma.

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