Advances in the research of osteosarcoma stem cells and its related genes

Zhang, Weifei; Wei, Liangchen; Weng, Jian; Yu, Fei; Qin, Haotian; Wang, Deli; Zeng, Hui

doi:10.1002/cbin.11752

Cited by 6 publications

(3 citation statements)

References 91 publications

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“…The theory of tumor stem cells posits that tumors are maintained by stem cells, and the incomplete eradication of tumor stem cells is the cause of tumor drug resistance and recurrence ( 7 ). Targeting cancer stem cells (CSCs) may represent the future treatment direction of OS ( 8 ). osteosarcoma CSCs have been identified as the main cause of recurrence and metastasis ( 9 , 10 ).…”

Section: Introductionmentioning

confidence: 99%

Construction of a novel mRNAsi-related risk model for predicting prognosis and immunotherapy response in osteosarcoma

Li¹,

Jin²,

Lu³

et al. 2023

Ann Transl Med

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Background Targeting cancer stem cells (CSC) may represent a future therapeutic direction for osteosarcoma (OS), which mainly relies on the identification of CSC markers. This study aimed to classify OS based on messenger ribonucleic acid (mRNA) stemness indices (mRNAsi) and construct a mRNAsi-related risk model to predict the prognosis of OS. Methods The one-class logistic regression (OCLR) algorithm was applied to the RNA- sequencing (seq) data of human embryonic stem cells (hESC) and induced pluripotent stem cell (iPSC) lines to calculate mRNAsi. Weighted gene co-expression network analysis (WGCNA) was performed on data obtained from the TARGET database to screen the mRNAsi-related genes. Univariate Cox regression analysis was implemented to screen mRNAsi-related genes with prognostic significance for consensus clustering of OS. The least absolute shrinkage and selection operator (LASSO) and COX regression analysis were conducted to construct a risk model based on mRNAsi-related genes. Results Six gene modules were identified in the TARGET database. The yellow module showed the strongest negative correlation with mRNAsi and the strongest significant positive correlation with the immune score and stromal score. OS was divided into three molecular subtypes with significant survival differences based on 73 mRNAsi-related genes with prognostic value for OS. The survival rate was ranked as C3 < C1 < C2 from low to high. The levels of immune components in C2 was significantly higher than those in C1 and C3. HSD11B2, GBP1, RNF130, APBB1IP, and NPC2 in the yellow module were used as variables for building the mRNAsi-related risk model. The survival rate of the high-risk group (as defined by this model) was significantly higher than that of the low-risk group, and it had significant survival prediction ability in 28 types of cancer. In addition, the mRNAsi-related risk model was superior to the Tumor Immune Dysfunction and Exclusion (TIDE) model in predicting the prognosis and immunotherapy response in all three immunotherapy cohorts. Conclusions This study classified OS and constructed a mRNAsi-related risk model based on mRNAsi-related genes, which provides a potential tool for more accurate risk stratification of OS and prediction of immunotherapy response.

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Section: Introductionmentioning

confidence: 99%

Construction of a novel mRNAsi-related risk model for predicting prognosis and immunotherapy response in osteosarcoma

Li¹,

Jin²,

Lu³

et al. 2023

Ann Transl Med

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“…The 5-year survival rate for patients without metastases is approximately 65–70 percent when limb salvage surgery and neoadjuvant chemotherapy are combined [ 3 ]. Because osteosarcoma has such a dismal prognosis following metastasis, new therapeutic approaches are desperately needed [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

DNMT3A Regulates miR-149 DNA Methylation to Activate NOTCH1/Hedgehog Pathway to Promote the Development of Junctional Osteosarcoma

Cheng

Wang

2022

BioMed Research International

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Purpose. To investigate the DNMT3A/miR-149/NOTCH1/Hedgehog axis regulating the development of osteosarcoma. Methods. First, microRNA and mRNA expression microarrays were downloaded from the GEO database for osteosarcoma and differentially expressed microRNAs were analyzed. Subsequently, we collected cancerous tissues and corresponding paracancerous tissues from 42 osteosarcoma patients and examined the expression levels of miR-149, DNMT3A, and NOTCH1 in the samples. Subsequently, miR-149 was overexpressed in osteosarcoma cells to detect cell proliferation and metastatic ability changes. We then queried the methylation level of the miR-149 promoter on the bioinformatics website and verified it by experiment. We further demonstrated the expression level of miR-149 with NOTCH1 using a dual luciferase assay and confirmed the role of NOTCH1 on osteosarcoma cell growth and metastasis by functional rescue assay. Finally, we detected the activation level of the Hedgehog/catenin signaling pathway by WB and immunofluorescence. Results. miR-149 was significantly low expressed in osteosarcoma tissues and cells, while DNMT3A and NOTCH1 were highly expressed in osteosarcoma tissues and cells, and negatively correlated with miR-149 expression levels. Overexpression of miR-149 significantly inhibited the growth and metastasis of osteosarcoma cells in vitro and in vivo, and we found that DNMT3A could promote the methylation modification of the miR-149 promoter, thereby inhibiting the expression of miR-149. Subsequently, the experimental results showed that miR-149 could target negative regulation of NOTCH1, and further overexpression of NOTCH1 in cells with high miR-149 expression could promote the growth and metastasis of osteosarcoma cells in vitro. Conclusion. The methyltransferase DNMT3A suppresses miR-149 expression by promoting methylation modification of the miR-149 promoter, resulting in elevated expression levels of NOTCH1 in cells, therefore exacerbating activation of the Hedgehog signaling pathway and therefore exacerbating the development and progression of osteosarcoma.

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“…5,6 Apoptosis, autophagy, necrosis, and pyroptosis are regular forms of cell death. 7 Ferroptosis, a new form of cell death, is mediated by intracellular iron and is clearly distinguished from other forms of cell death forms. 8,9 Recently, emerging evidence has highlighted that aberrant cellular iron metabolism can induce overproduction of reactive oxygen species (ROS) and trigger lipid peroxidation (LPO).…”

Section: Introductionmentioning

confidence: 99%

Curcumin induces ferroptosis and apoptosis in osteosarcoma cells by regulating Nrf2/GPX4 signaling pathway

Yuan,

Fan,

Zhu

et al. 2023

Exp Biol Med (Maywood)

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Curcumin, an antitumor agent, has been shown to inhibit cell growth and metastasis in osteosarcoma. However, there is no evidence of curcumin and its regulation of cell ferroptosis and nuclear factor E2–related factor 2 (Nrf2)/glutathione peroxidase 4 (GPX4) signaling pathways in osteosarcoma. This study aimed to investigate the effects of curcumin on osteosarcoma both in vitro and in vivo. To explore the effects and mechanisms of curcumin on osteosarcoma, cells (MNNG/HOS and MG-63) and xenograft mice models were established. Cell viability, cell apoptosis rate, cycle distribution, cell migration, cell invasion, reactive oxygen species, malonaldehyde and glutathione abilities, and protein levels were detected by cell counting kit-8, flow cytometry, wound healing, transwell assay, respectively. Nrf2 and GPX4 expressions were detected using an immunofluorescence assay. Nrf2/GPX4-related protein levels were detected using western blotting. The results showed that curcumin effectively decreased cell viability and increased apoptosis rate. Meanwhile, curcumin inhibited tumor volume in the xenograft model, and Nrf2/GPX4-related protein levels were also altered. Interestingly, the effects of curcumin were reversed by liproxstatin-1 (an effective inhibitor of ferroptosis) and bardoxolone-methyl (an effective activator of Nrf2). Our results indicate that curcumin has therapeutic effects on osteosarcoma cells and a xenograft model by regulating the expression of the Nrf2/GPX4 signaling pathway.

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Advances in the research of osteosarcoma stem cells and its related genes

Cited by 6 publications

References 91 publications

Construction of a novel mRNAsi-related risk model for predicting prognosis and immunotherapy response in osteosarcoma

Construction of a novel mRNAsi-related risk model for predicting prognosis and immunotherapy response in osteosarcoma

DNMT3A Regulates miR-149 DNA Methylation to Activate NOTCH1/Hedgehog Pathway to Promote the Development of Junctional Osteosarcoma

Curcumin induces ferroptosis and apoptosis in osteosarcoma cells by regulating Nrf2/GPX4 signaling pathway

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