Relationship Between P15 Gene Mutation and Formation and Metastasis of Malignant Osteosarcoma

Yu, ChangShui; Wang, Wenbo

doi:10.12659/msm.895022

Cited by 12 publications

(8 citation statements)

References 23 publications

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“…Invasion, which generally leads to metastasis, can be used to predict tumor malignancy (32). Previous research reported that early metastasis (particularly pulmonary metastasis) remains as the main cause of mortality in ~40% of patients with osteosarcoma (33). The results of Transwell assays demonstrated that salidroside significantly inhibited the invasive ability of osteosarcoma cells in a concentration-dependent manner.…”

Section: Discussionmentioning

confidence: 99%

Salidroside suppresses the growth and invasion of human osteosarcoma cell lines MG63 and U2OS in vitro by inhibiting the JAK2/STAT3 signaling pathway

Huang

Lin

et al. 2019

Int J Oncol

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Previous research has reported that salidroside exerts antitumor properties on numerous types of tumor cells; however, its effect on osteosarcoma cells remains unknown. The present study aimed to investigate the effects of salidroside on the viability, apoptosis and invasion of osteosarcoma cells in vitro , and determine the underlying mechanism of action. The results of an MTT revealed that salidroside suppressed the viability of osteosarcoma cells (MG63 and U2OS cells) in a time- and concentration-dependent manner. The results of cell morphological analysis (profile observations and Hoechst 33258 staining) and the detection of apoptosis by flow cytometry further indicated that the decrease in osteosarcoma cell viability induced by salidroside was associated with cell apoptosis. Western blot analysis not only confirmed these results but also suggested that salidroside induced the apoptosis of osteosarcoma cells by activating the caspase-9-dependent apoptotic pathway. In addition, we reported that salidroside induced G 0 /G 1 phase arrest and suppressed the invasion of osteosarcoma cells, as measured by flow cytometric cell cycle analysis and a Transwell invasion assay, respectively. Western blot analysis confirmed the aforementioned results. Furthermore, our findings demonstrated that salidroside induced the apoptosis, G 0 /G 1 phase arrest and suppressed the invasion of osteosarcoma cells by inhibiting the janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway, as determined by western blot analysis. In summary, the findings of the present study suggested that salidroside may inhibit the progression of osteosarcoma by suppressing the growth and invasion of osteosarcoma cells. Furthermore, the investigations into the underlying mechanism demonstrated that salidroside exerted notable antitumor activity in osteosarcoma cells by inhibiting the JAK2/STAT3 signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Salidroside suppresses the growth and invasion of human osteosarcoma cell lines MG63 and U2OS in vitro by inhibiting the JAK2/STAT3 signaling pathway

Huang

Lin

et al. 2019

Int J Oncol

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“…THPO, specifically, is responsible for the emergence of hemangioblasts and the migration of hematopoietic cells. MPL mutations are prevalent in AML making it apparent the ligand/receptor complex plays a key role in malignant hematopoiesis [18]. Bcl-xL is upregulated after AML1-ETO expression and it is maintained at these levels via the THPO/MPL signaling pathway, inducing the overexpression of MPL.…”

Section: Transcriptional Dysregulation and Different Transcriptional ...mentioning

confidence: 99%

“…Bcl-xL is upregulated after AML1-ETO expression and it is maintained at these levels via the THPO/MPL signaling pathway, inducing the overexpression of MPL. In the presence of Bcl-xL, the THPO/MPL complex is facilitates cell cycle re-entry and the significant correlation between Bcl-xL and MPL is indicative of an active THPO/MPL/Bcl-xL pathway in leukemic t(8;21)-positive cells [18].…”

Section: Transcriptional Dysregulation and Different Transcriptional ...mentioning

confidence: 99%

“…AML1-ETO also affects the THPO/MPL signaling pathway through upregulating the expression of Bcl-xL resulting in the increase of MPL. This affects many things like cell cycle re-entry, emergence of hemangioblasts, and the migration of hematopoietic cells leading to AML [18]. Bcl-xL could be a potential target for therapeutic approaches but there are some questions about specificity and differentiating between normal and AML states.…”

Section: Future Implications and Therapeutic Approaches For Runx1/run...mentioning

confidence: 99%

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Mechanisms of AML1-ETO Induced Transcription Factor Dysregulation, Epigenetic Modification, and Immune System Evasion in Pre-Leukemic Stem Cells

Kaveen Thanaraj,

Busanelli

2024

URNCST Journal

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Introduction: Acute myeloid leukemia is a cancer of the bone marrow with a low survival rate of 15% among elderly individuals due to its rapid progression and lack of available treatment. Understanding different transcription factors that may contribute to the progression of leukemia and leukemogenesis is crucial in developing effective treatment plans to control the advancement of AML within patients. This paper aims to conduct a literature review where primary articles contain evidence exhibiting a link between transcriptional dysregulation in genes that code for regulatory proteins involved in cell cycle progression and irregularity present in pre-leukemic stem cells. Methods: Databases Medline and Embase were searched using keywords "leukemogenesis," "pre-leukemic," "AML1", "Acute myeloid leukemia", and "AML-ETO". Only studies written in the English language that were published in peerreviewed journals and human post-mortem/pathophysiological studies were considered in the review. The search emphasized studies published between 1998-2023 to include recent literature reported in the respective field. Results: AML1 regulates the expression of cell cycle checkpoint regulating proteins and proteins involved in hematopoietic differentiation in order to prevent asymmetric production of mutated hematopoietic stem cells (HSCs) as well as defective cells from progressing through the cycle via apoptosis. Chromosomal translocations allow for the AML1 gene to be fused with ETO, causing issues with transcriptional regulation, which work to continuously repress the function of this complex, preventing the transcription of necessary proteins needed to regulate the cell cycle. Implications: The fusion of AML1 and ETO causes the deregulation of the transcription complex, repressing the binding of transcription factors. This means that defective cells within hematopoiesis are not subject to apoptosis, leading to the production of pre-leukemic stem cells, which contributes to leukemogenesis. Understanding the mechanisms leading to the production of pre-leukemic stem cells opens up possible treatment channels from pharmacological and physiological approaches. In addition, leukemia can be identified and diagnosed at an earlier stage by identifying AML1 in relation to ETO as a precursor for AML.

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“…In addition, there is a strong association between the presence of the mutated p15 gene and the propensity for lung metastasis. 5 By adding a ligand that binds to cells that express the mutated p15 gene, via the above mechanism, early identification of metastasis or of the metastatic potential of the tumor may be achieved. 4 Superparamagnetic iron oxide (ie, metallic) nanoparticles or quantum dot nanocrystals have been studied in a similar fashion as contrast agents for targeted magnetic resonance imaging.…”

Section: Diagnostic Applicationsmentioning

confidence: 99%

Applied Nanotechnology and Nanoscience in Orthopedic Oncology

Savvidou¹,

Bolia²,

Chloros³

et al. 2016

Orthopedics

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Nanomedicine is based on the fact that biological molecules behave similarly to nanomolecules, which have a size of less than 100 nm, and is now affecting most areas of orthopedics. In orthopedic oncology, most of the in vitro and in vivo studies have used osteosarcoma or Ewing sarcoma cell lineages. In this article, tumor imaging and treatment nanotechnology applications, including nanostructure delivery of chemotherapeutic agents, gene therapy, and the role of nano-selenium-coated implants, are outlined. Finally, the potential role of nanotechnology in addressing the challenges of drug and radiotherapy resistance is discussed. [Orthopedics. 2016; 39(5):280-286.].

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Relationship Between P15 Gene Mutation and Formation and Metastasis of Malignant Osteosarcoma

Cited by 12 publications

References 23 publications

Salidroside suppresses the growth and invasion of human osteosarcoma cell lines MG63 and U2OS in vitro by inhibiting the JAK2/STAT3 signaling pathway

Salidroside suppresses the growth and invasion of human osteosarcoma cell lines MG63 and U2OS in vitro by inhibiting the JAK2/STAT3 signaling pathway

Mechanisms of AML1-ETO Induced Transcription Factor Dysregulation, Epigenetic Modification, and Immune System Evasion in Pre-Leukemic Stem Cells

Applied Nanotechnology and Nanoscience in Orthopedic Oncology

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