RETRACTED ARTICLE: Ras-ERK1/2 signalling promotes the development of osteosarcoma through regulation of H4K12ac through HAT1

Zhang, Jingzhe; Liu, Meihan; Liu, Wanguo; Wang, Wenjun

doi:10.1080/21691401.2019.1593857

Cited by 11 publications

(10 citation statements)

References 34 publications

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“…The results of KEGG analysis showed that the DEmRNAs are widely involved in the "PI3K-AKT," "MAPK," and "Ras" pathways. These pathways have been confirmed as regulating the progress of OSA, [29][30][31][32] which indicates that the model we built has research value. In addition, we constructed a PPI network and identified 10 hub genes.…”

mentioning

confidence: 61%

Circular RNA-Related CeRNA Network and Prognostic Signature for Patients with Osteosarcoma

Gu¹,

Duan²,

Liu³

et al. 2021

CMAR

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Introduction Osteosarcoma (OSA) is characterized by its relatively high morbidity in children and adolescents. Patients usually have advanced disease at the time of diagnosis, resulting in poor outcomes. This study focused on building a circular RNA-based ceRNA network to develop a reliable model for OSA risk prediction. Methods We used the Gene Expression Omnibus (GEO) datasets to explore the expression patterns of circRNA, miRNA, and mRNA in OSA. The prognostic value of circRNA host genes was assessed with data from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database using Kaplan–Meier survival analysis. We established a circRNA-related ceRNA network and annotated its biological functions. Next, we developed a prognostic risk signature based on mRNAs extracted from the ceRNA network. We also developed a prognostic model and constructed a nomogram to enhance the prediction of OSA prognosis. Results We identified 166 DEcircRNAs, 233 DEmiRNAs, and 1317 DEmRNAs and used them to create a circRNA-related ceRNA network. We then established a prognostic risk model consisting of four genes (MLLT11, TNFRSF11B, SLC7A7, and PARVA). Moreover, we found that inhibition of MLLT11 and SLC7A7 blocked OSA cell proliferation and migration in in vitro experiments. Conclusion Our study identifies crucial prognostic genes and provides a circRNA-related ceRNA network for OSA, which will contribute to the elucidation of the molecular mechanisms underlying the oncogenesis and development of OSA.

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confidence: 61%

Circular RNA-Related CeRNA Network and Prognostic Signature for Patients with Osteosarcoma

Gu¹,

Duan²,

Liu³

et al. 2021

CMAR

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“…HAT1 has also been shown to induce apoptosis by upregulating Fas expression in lung cancer cells 46 . In addition, Ras-ERK1/2 signaling has been shown to promote the development of osteosarcoma through the regulation of H4K12Acetyl, via HAT1 47 . We showed that the loss of HAT1 expression was associated with the development of resistance to BRAFi, such as vemurafenib and dabrafenib.…”

Section: Discussionmentioning

confidence: 99%

Loss of HAT1 expression confers BRAFV600E inhibitor resistance to melanoma cells by activating MAPK signaling via IGF1R

et al. 2020

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BRAF inhibitors (BRAFi) have been approved for the clinical treatment of BRAF-mutant metastatic melanoma. Although initial responses to BRAFi are generally favorable, acquired BRAFi resistance emerges rapidly, resulting in treatment failure. Only some of the underlying mechanisms responsible for BRAFi resistance are currently understood. Here, we showed that the genetic inhibition of histone acetyltransferase 1 (HAT1) in BRAF-mutant melanoma cells resulted in BRAFi resistance. Using quantitative immunofluorescence analysis of patient sample pairs, consisting of pre-treatment along with matched progressed BRAFi + MEKi-treated melanoma samples, HAT1 downregulation was observed in 7/ 11 progressed samples (~63%) in comparison with pre-treated samples. Employing NanoString-based nCounter PanCancer Pathway Panel-based gene expression analysis, we identified increased MAPK, Ras, transforming growth factor (TGF)-β, and Wnt pathway activation in HAT1 expression inhibited cells. We further found that MAPK pathway activation following the loss of HAT1 expression was partially driven by increased insulin growth factor 1 receptor (IGF1R) signaling. We showed that both MAPK and IGF1R pathway inhibition, using the ERK inhibitor SCH772984 and the IGF1R inhibitor BMS-754807, respectively, restored BRAFi sensitivity in melanoma cells lacking HAT1. Collectively, we show that the loss of HAT1 expression confers acquired BRAFi resistance by activating the MAPK signaling pathway via IGF1R.

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“…Therefore, lncRNA PCAT6, which was reported to regulate miRNA levels, affected the expression of MDM2 possibly through miRNAs, ( 56 – 58 ). Additionally, in MG63 cells, MDM2 was regulated by proteins including Ras-ERK1/2 signaling or GRIM-19 ( 59 , 60 ). Thus, MDM2 could be regulated by lncRNA PCAT6 possibly attributing to the regulation of lncRNA PCAT6 on the upstream proteins of MDM2.…”

Section: Discussionmentioning

confidence: 99%

Long non‑coding RNA PCAT6 promotes the development of osteosarcoma by increasing MDM2 expression

Guan

Zheng

2020

Oncol Rep

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Osteosarcoma is a severe malignant tumor. Several studies indicated that lncRNA prostate cancer-associated transcript 6 (PCAT6) promoted the development of multiple types of cancers. Studies have also revealed that MDM2 could aggravate tumor symptoms inhibiting P53 expression. However, whether lncRNA PCAT6 could affect the proliferation and metastasis of osteosarcoma cells by regulating P53 expression is unclear. The present study established lncRNA PCAT6-overexpressing osteosarcoma cells. Cell Counting Kit-8, wound healing and Transwell assays were performed to detect the change in proliferation, migration and invasion of these cells, respectively. Subsequently, E3 ubiquitin-protein ligase Mdm2 (MDM2), P53 and P21 expression were determined using western blotting. Finally, MDM2 expression was inhibited and the proliferation, migration and invasion of these cells was determined again. The present study found that the proliferation, migration and invasion of osteosarcoma cells increased following overexpression of lncRNA PCAT6. MDM2 expression was upregulated while the levels of P53 and P21 decreased following overexpression of lncRNA PCAT6. However, the proliferation, migration and invasion of osteosarcoma cells were inhibited following MDM2 knockdown. Additionally, P53 and P21 was rescued following MDM2 knockdown. To conclude, lncRNA PCAT6 promoted the proliferation, migration and invasion of osteosarcoma cells by promoting the expression of MDM2 and suppressing the expression of P53 and P21.

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RETRACTED ARTICLE: Ras-ERK1/2 signalling promotes the development of osteosarcoma through regulation of H4K12ac through HAT1

Cited by 11 publications

References 34 publications

Circular RNA-Related CeRNA Network and Prognostic Signature for Patients with Osteosarcoma

Circular RNA-Related CeRNA Network and Prognostic Signature for Patients with Osteosarcoma

Loss of HAT1 expression confers BRAFV600E inhibitor resistance to melanoma cells by activating MAPK signaling via IGF1R

Long non‑coding RNA PCAT6 promotes the development of osteosarcoma by increasing MDM2 expression

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