Identification of differentially expressed genes in MG63 osteosarcoma cells with drug‑resistance by microarray analysis

Chen, Rui; Huang, Lihong; Gao, Yiyao; Yang, Jinru; Wang, Yan

doi:10.3892/mmr.2018.9774

Cited by 7 publications

(7 citation statements)

References 25 publications

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“…Furthermore, molecular docking results showed that vincristine, dexamethasone, and vinblastine all bound well to the key targets RUNX2, OMD, and CD4. Vincristine, dexamethasone, and vinblastine are common drugs used to treat OS (Boscoboinik et al, 1994;Ahlström et al, 2005;Chen et al, 2019). These results suggested that these five key targets could be potential targets for OS treatment.…”

Section: Discussionmentioning

confidence: 90%

Identification of therapeutic targets for osteosarcoma by integrating single-cell RNA sequencing and network pharmacology

Wang

Qin²,

Gao³

et al. 2023

Front. Pharmacol.

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Background: Osteosarcoma (OS) is a common primary tumor with extensive heterogeneity. In this study, we used single-cell RNA sequencing (scRNA-seq) and network pharmacology to analyze effective targets for Osteosarcoma treatment.Methods: The cell heterogeneity of the Osteosarcoma single-cell dataset GSE162454 was analyzed using the Seurat package. The bulk-RNA transcriptome dataset GSE36001 was downloaded and analyzed using the CIBERSORT algorithm. The key targets for OS therapy were determined using Pearson’s correlation analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed on key targets. The DeepDR algorithm was used to predict potential drugs for Osteosarcoma treatment. Molecular docking analysis was performed to verify the binding abilities of the predicted drugs and key targets. qRT-PCR assay was used to detect the expression of key targets in osteoblasts and OS cells.Results: A total of 21 cell clusters were obtained based on the GSE162454 dataset, which were labeled as eight cell types by marker gene tagging. Four cell types (B cells, cancer-associated fibroblasts (CAFs), endothelial cells, and plasmocytes) were identified in Osteosarcoma and normal tissues, based on differences in cell abundance. In total, 17 key targets were identified by Pearson’s correlation analysis. GO and KEGG analysis showed that these 17 genes were associated with immune regulation pathways. Molecular docking analysis showed that RUNX2, OMD, and CD4 all bound well to vincristine, dexamethasone, and vinblastine. The expression of CD4, OMD, and JUN was decreased in Osteosarcoma cells compared with osteoblasts, whereas RUNX2 and COL9A3 expression was increased.Conclusion: We identified five key targets (CD4, RUNX2, OMD, COL9A3, and JUN) that are associated with Osteosarcoma progression. Vincristine, dexamethasone, and vinblastine may form a promising drug–target pair with RUNX2, OMD, and CD4 for Osteosarcoma treatment.

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Section: Discussionmentioning

confidence: 90%

Identification of therapeutic targets for osteosarcoma by integrating single-cell RNA sequencing and network pharmacology

Wang

Qin²,

Gao³

et al. 2023

Front. Pharmacol.

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“…With the development of new therapeutic technologies, the survival rate of patients with OS has markedly increased. However, the overall outcome of patients with OS remains poor due to drug or multidrug resistance (19,20). Thus, the study of the mechanisms responsible for the development of OS and the identification of novel effective treatable methods for patients with OS is crucial.…”

Section: Discussionmentioning

confidence: 99%

Knockdown of Ski decreases osteosarcoma cell proliferation and migration by suppressing the PI3K/Akt signaling pathway

et al. 2019

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Ski, an evolutionary conserved protein, is involved in the development of a number of tumors, such as Barrett's esophagus, leukemia, colorectal cancer, gastric cancer, pancreatic cancer, hemangiomas and melanoma. However, studies on the functions of Ski in osteosarcoma (OS) are limited. In this study, firstly the differential expression of Ski in OS tissues and osteochondroma tissues was detected, and the expression of Ski in both human OS cell lines (MG63 and U2OS) and normal osteoblasts (hFoB1.19) was then detected. The results demonstrated that Ski expression was significantly upregulated in both human OS tissues and cell lines. The results led us to hypothesize that Ski may play an essential role in the pathological process of OS. Thus, Ski specific small interfere RNA (Ski-siRNA) was used. The results revealed that OS cell proliferation was markedly inhibited following the knockdown of Ski, which was identified by CCK8 assay, EdU staining and cell cycle analysis. In addition, OS cell migration was significantly suppressed following Ski knockdown, which was identified by wound healing assay. Moreover, the protein levels of p-PI3K and p-Akt in OS cells declined prominently following Ski knockdown. On the whole, the findings of this study revealed that Ski expression was significantly upregulated in OS tissue and OS cells. The knockdown of Ski decreased OS cell proliferation and migration, which was mediated by blocking the PI3K/Akt signaling pathway. Thus, Ski may act as a tumor promoter gene in tumorigenesis, and Ski may prove to be a potential therapeutic target for the treatment of OS.

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“…MG-63 and Saos-2 cells were provided by the China Center for Type Culture Collection as in our previous study ( Shu et al, 2020 ). MG-63 and Saos-2 cells were cultured in RPMI‑1640 and McCoy’s 5A medium (Gibco; Thermo Fisher Scientific, Inc., Waltham, MA, USA), respectively, supplemented with 10% FBS (Gibco; Thermo Fisher Scientific, Inc., Waltham, MA, USA), 1% L‑glutamine, and 1% penicillin‑streptomycin sulfate (Thermo Fisher Scientific, Inc., Waltham, MA, USA) at 37 °C in a 5% CO 2 humidity-controlled incubator ( Chen et al, 2019 ; Zhou et al, 2016 ).…”

Section: Methodsmentioning

confidence: 99%

Analysis of microRNA expression in CD133 positive cancer stem‑like cells of human osteosarcoma cell line MG-63

Xiong

Liu

et al. 2021

PeerJ

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Osteosarcoma (OS) is a primary malignant tumor of bone occurring in young adults. OS stem cells (OSCs) play an important role in the occurrence, growth, metastasis, drug resistance and recurrence of OS. CD133 is an integral membrane glycoprotein, which has been identified as an OSC marker. However, the mechanisms of metastasis, chemoresistance, and progression in CD133(+) OSCs need to be further explored. In this study, we aim to explore differences in miRNA levels between CD133(+) and CD133(−) cells from the MG-63 cell line. We found 20 differentially expressed miRNAs (DEmiRNAs) (16 upregulated and 4 downregulated) in CD133(+) cells compared with CD133(−) cells. Hsa-miR-4485-3p, hsa-miR-4284 and hsa-miR-3656 were the top three upregulated DEmiRNAs, while hsa-miR-487b-3p, hsa-miR-493-5p and hsa-miR-431-5p were the top three downregulated DEmiRNAs. In addition, RT-PCR analysis confirmed that the expression levels of hsa-miR-4284, hsa-miR-4485-3p and hsa-miR-3656 were significantly increased, while the expression levels of hsa-miR-487b-3p, hsa-miR-493-5p, and hsa-miR-431-5p were significantly decreased in CD133(+) cells compared with CD133(−) cells. Moreover, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that predicted or validated target genes for all 20 DEmiRNAs or the selected 6 DEmiRNAs participated in the “PI3K-Akt signaling pathway,” “Wnt signaling pathway,” “Rap1 signaling pathway,” “Cell cycle” and “MAPK signaling pathway”. Among the selected six DEmiRNAs, miR-4284 was especially interesting. MiR-4284 knockdown significantly reduced the sphere forming capacity of CD133(+) OS cells. The number of invasive CD133(+) OS cells was markedly decreased after miR-4284 knockdown. In addition, miR-4284 knockdown increased the p-β-catenin levels in CD133(+) OS cells. In conclusion, RNA-seq analysis revealed DEmiRNAs between CD133(+) and CD133(−) cells. MiRNAs might play significant roles in the function of OSCs and could serve as targets for OS treatment. MiR-4284 prompted the self-renewal and invasion of OSCs. The function of miR-4284 might be associated with the Wnt signaling pathway.

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Identification of differentially expressed genes in MG63 osteosarcoma cells with drug‑resistance by microarray analysis

Cited by 7 publications

References 25 publications

Identification of therapeutic targets for osteosarcoma by integrating single-cell RNA sequencing and network pharmacology

Identification of therapeutic targets for osteosarcoma by integrating single-cell RNA sequencing and network pharmacology

Knockdown of Ski decreases osteosarcoma cell proliferation and migration by suppressing the PI3K/Akt signaling pathway

Analysis of microRNA expression in CD133 positive cancer stem‑like cells of human osteosarcoma cell line MG-63

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