miR-1301/TRIAP1 Axis Participates in Epirubicin-Mediated Anti-Proliferation and Pro-Apoptosis in Osteosarcoma

Liu, Yu; Meng, Min; Bao, Yun; Zhang, Chao; Gao, Bei; Sa, Rina; Luo, Wenyuan

doi:10.3349/ymj.2019.60.9.832

Cited by 13 publications

(23 citation statements)

References 31 publications

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“…Further, in beta-estradiol treatment process of osteosarcoma, TCF7L2 was observed reduce the expression with other members involved in Wnt/beta-catenin canonical signaling pathway [61]. TRIAP1 (TP53 regulated inhibitor of apoptosis 1) is a notable inhibitor of apoptosis controlled by TP53 and an available target by epirubicin in osteosarcoma [62]. CBS, cystathionine β-synthase, was associated with homocysteine metabolism, remethylation metabolism, the generation of H 2 S, drug resistance, oxidative stress and ferroptosis [63][64][65].…”

Section: Discussionmentioning

confidence: 96%

Identification of a Programmed Cell Death-related Signature for Prediction of Osteosarcoma

Lin

et al. 2021

Preprint

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Background: This study aims to perform bioinformatics analysis of programmed cell death-related genes (PCDGs) in osteosarcoma, and to construct a multi-gene signature for predicting the prognosis.Methods: The functional enrichment analysis was applied for prognostic PCDGs, and PPI network as well as drug-gene interactions were constructed. In order to set up the prognosis evaluation system, we established a prognosis model by integrating PCDGs. The Least Absolute Shrinkage and Selection Operator (LASSO) logistic regression analysis as well as the multivariate Cox proportional hazard regression analysis were used to construct the five-genes signature (MUC1, TCF7L2, TGFB2, TRIAP1, CBS) for prediction in Gene Expression Omnibus (GEO) cohort. According to the median risk score, survival analysis was conducted to evaluate the prognostic value of the risk score in GEO cohort. Next, by combining other clinic-pathological independent prognostic factor, stage at diagnosis, a nomogram was established to predict individual survival probability. Result: GO analysis showed that the 15 prognostic PCDGs were mainly enriched in apoptotic signaling pathway, regulation of secretion and p53 signaling pathway. KEGG analysis showed that aforesaid genes were mainly related to PI3K-Akt signaling pathway, diverse neoplasms signaling pathway and hepatitis B. Drug-gene interactions displayed available drugs for influencing osteosarcoma via programmed cell death, such as adalimumab, tacrolimus and sirolimus. The risk score was constructed based on 5 genes and patients were significantly divided into high-risk and low-risk groups according to overall survival. In multivariate Cox regression analysis, risk score was still an independent prognostic factor (HR = 2.526, 95% CI = 1.597−3.994, P < 0.001). Cumulative curve showed that low-risk score patients were significantly had better prognosis than that of patients with high-risk score (P < 0.001). The external independent TARGET cohort proved the validity of risk score model and the nomograph.Conclusion: From the facet of programmed cell death, we provided a multi-gene signatureand the nomograph for the prognostic predictors of osteosarcoma patients, and available drugs displayed may provide promising treatment strategies.

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Section: Discussionmentioning

confidence: 96%

Identification of a Programmed Cell Death-related Signature for Prediction of Osteosarcoma

Lin

et al. 2021

Preprint

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“…Hence, we have concluded that miR-539 can inhibit the growth of OS by downregulating the expression of TRIAP1 and that the possible molecular mechanism involves miR-539 binding to the 3' UTR of TRIAP1 and destroying the apoptosis inhibition of TRIAP1 by activating its downstream genes, such as p53, p21, apaf1 and caspase9. However, the TRIAP1 gene is regulated by the TP53 gene [13], miR-1301 [20], miR-18a [15], and miR-320b [14], and miR-539 can regulate the expression of SP1 [32], TWIST1 [33], and DCLK1 [26]. In this study, we only investigated the effect of miR-539 on TRIAP1 and OS, but more details need to be examined and further research should be undertaken.…”

Section: Discussionmentioning

confidence: 99%

The Effect of miR-539 Regulating TRIAP1 on the Apoptosis, Proliferation, Migration and Invasion of Osteosarcoma Cells

Liu

Zhang

Yang

et al. 2021

Preprint

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Objective The purpose of this study is to explore the effect of miRNA-539 on osteosarcoma and the underlying mechanism, so as to find a new method for early diagnosis and treatment of osteosarcoma.Method miRNA-539 mimics was transfected into osteosarcoma cells 143b and MG-63 and upregulated the expression of miR-539. QT-PCR was used to detect transfection efficacy. CCK-8 method was used to detect proliferation of 143b and MG-63 osteosarcoma cells and flow cytometry was used to detect the apoptosis of osteosarcoma cells 143b and MG-63. Wound-healing test and Transwell test were used to detect the migration and invasion ability of osteosarcoma cells. TRIAP1 was found to be the potential target gene of miRNA-539 by online bioinformatics software and the expression level of TRIAP1 in osteosarcoma cells overexpressing miRNA-539 was detected by qT-PCR. Western blot was used to detect the level of expression of TRIAP1 and its downstream genes (p53, p21, apaf1 and caspase9) in osteosarcoma cells 143b and MG63 transfected with miR-539 mimics or miR-539 mimics-NC. A model of osteosarcoma subcutaneously transplanted in nude mice was constructed to observe the effect of miRNA-539 on the growth rate of osteosarcoma in vivo.Results After transfection of miRNA-539 mimics in osteosarcoma cells 143b and MG63, the proliferation level, migration ability, and invasion ability of the osteosarcoma cells were significantly lower than that in the control group, and the apoptosis level was significantly higher than that in the control group (P <0.01). The dual luciferase reporter confirmed that TRIAP1 was the target of miR-539, and the expression level of TRIAP1 in 143b and MG63 transfected with miRNA-539 mimics was proved to be significantly lower than that in the control group (P<0.01).The western blot showed the expression of genes targeted by TRIAP1 was upregulated when the expression of TRIAP1 was downregulated. In vivo, the osteosarcoma growth rate in the miRNA-539 mimics group was significantly slower than that in the control group (P<0.01).Conclusion MiRNA-539 may inhibit the cell proliferation, migration and invasion of osteosarcoma cells and promote the apoptosis of osteosarcoma cells by targeting on TRIAP1.

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“…Hence, we have concluded that miR-539 can inhibit the growth of OS by downregulating the expression of TRIAP1 and that the possible molecular mechanism involves miR-539 binding to the 3' UTR of TRIAP1 and destroying the apoptosis inhibition of TRIAP1 by activating its downstream genes, such as p53, p21, apfa1 and caspase9. However, the TRIAP1 gene is regulated by the TP53 gene [13], miR-1301 [20], miR-18a [15], and miR-320b [14], and miR-539 can regulate the expression of SP1 [32], TWIST1 [33], and DCLK1 [26]. In this study, we only investigated the effect of miR-539 on TRIAP1 and OS, but more details need to be examined and further research should be undertaken.…”

Section: Discussionmentioning

confidence: 99%

The Effect of miR-539 Regulating TRIAP1 on the Apoptosis, Proliferation, Migration and Invasion of Osteosarcoma Cells

Liu

Zhang

Yang

et al. 2020

Preprint

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Objective The purpose of this study is to explore the effect of miRNA-539 on osteosarcoma and the underlying mechanism, so as to find a new method for early diagnosis and treatment of osteosarcoma. Method miRNA-539 mimics was transfected into osteosarcoma cells 143b and MG-63 and upregulated the expression of miR-539. QT-PCR was used to detect transfection efficacy. CCK-8 method was used to detect proliferation of 143b and MG-63 osteosarcoma cells and flow cytometry was used to detect the apoptosis of osteosarcoma cells 143b and MG-63. Wound-healing test and Transwell test were used to detect the migration and invasion ability of osteosarcoma cells. TRIAP1 was found to be the potential target gene of miRNA-539 by online bioinformatics software and the expression level of TRIAP1 in osteosarcoma cells overexpressing miRNA-539 was detected by qT-PCR. Western blot was used to detect the level of expression of TRIAP1 and its downstream genes (p53, p21, apfa1 and caspase9) in osteosarcoma cells 143b and MG63 transfected with miR-539 mimics or miR-539 mimics-NC. A model of osteosarcoma subcutaneously transplanted in nude mice was constructed to observe the effect of miRNA-539 on the growth rate of osteosarcoma in vivo. Results After transfection of miRNA-539 mimics in osteosarcoma cells 143b and MG63, the proliferation level, migration ability, and invasion ability of the osteosarcoma cells were significantly lower than that in the control group, and the apoptosis level was significantly higher than that in the control group (P < 0.01). The dual luciferase reporter confirmed that TRIAP1 was the target of miR-539, and the expression level of TRIAP1 in 143b and MG63 transfected with miRNA-539 mimics was proved to be significantly lower than that in the control group (P < 0.01).The western blot showed the expression of genes targeted by TRIAP1 was upregulated when the expression of TRIAP1 was downregulated. In vivo, the osteosarcoma growth rate in the miRNA-539 mimics group was significantly slower than that in the control group (P < 0.01). Conclusion MiRNA-539 may inhibit the cell proliferation, migration and invasion of osteosarcoma cells and promote the apoptosis of osteosarcoma cells by targeting on TRIAP1.

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miR-1301/TRIAP1 Axis Participates in Epirubicin-Mediated Anti-Proliferation and Pro-Apoptosis in Osteosarcoma

Cited by 13 publications

References 31 publications

Identification of a Programmed Cell Death-related Signature for Prediction of Osteosarcoma

Identification of a Programmed Cell Death-related Signature for Prediction of Osteosarcoma

The Effect of miR-539 Regulating TRIAP1 on the Apoptosis, Proliferation, Migration and Invasion of Osteosarcoma Cells

The Effect of miR-539 Regulating TRIAP1 on the Apoptosis, Proliferation, Migration and Invasion of Osteosarcoma Cells

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