Epigenetic Changes Associated with Osteosarcoma: A Comprehensive Review

Twenhafel, Luke; Moreno, DiAnna; Punt, Trista; Kinney, Madeline; Ryznar, Rebecca

doi:10.3390/cells12121595

Cited by 9 publications

(3 citation statements)

References 87 publications

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“…In cancer, the normal balance between active and repressive histone modification modifies the expression of oncogenes and tumor suppressor genes, leading to tumorigenesis. Recently, some evidence highlighted that deregulation of genes involved in these processes has been associated with OS tumorigenesis, progression and chemoresistance [ 383 ]. circLRP6, that is upregulated in OS and is associated with poor prognosis, was found to enhance the expression of histone deacetylase 4 (HDAC4) in OS cells via sponging miR-141-3p promoting cell proliferation, invasion [ 274 ].…”

Section: Cernets Involving Circrnasmentioning

confidence: 99%

Osteosarcoma in a ceRNET perspective

Mosca,

Alessio,

Di Paola

et al. 2024

J Biomed Sci

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Osteosarcoma (OS) is the most prevalent and fatal type of bone tumor. It is characterized by great heterogeneity of genomic aberrations, mutated genes, and cell types contribution, making therapy and patients management particularly challenging. A unifying picture of molecular mechanisms underlying the disease could help to transform those challenges into opportunities.This review deeply explores the occurrence in OS of large-scale RNA regulatory networks, denominated “competing endogenous RNA network” (ceRNET), wherein different RNA biotypes, such as long non-coding RNAs, circular RNAs and mRNAs can functionally interact each other by competitively binding to shared microRNAs. Here, we discuss how the unbalancing of any network component can derail the entire circuit, driving OS onset and progression by impacting on cell proliferation, migration, invasion, tumor growth and metastasis, and even chemotherapeutic resistance, as distilled from many studies. Intriguingly, the aberrant expression of the networks components in OS cells can be triggered also by the surroundings, through cytokines and vesicles, with their bioactive cargo of proteins and non-coding RNAs, highlighting the relevance of tumor microenvironment. A comprehensive picture of RNA regulatory networks underlying OS could pave the way for the development of innovative RNA-targeted and RNA-based therapies and new diagnostic tools, also in the perspective of precision oncology.

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Section: Cernets Involving Circrnasmentioning

confidence: 99%

Osteosarcoma in a ceRNET perspective

Mosca,

Alessio,

Di Paola

et al. 2024

J Biomed Sci

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“…Previous studies showed enhancement of the expression of the lysine-specific demethylases KDM1A, KDM2B, KDM4A, KDM6A, KDM6B in OS progression [31][32][33][34]. Recently, Twenhafel et al provided a comprehensive review of recent advances in the epigenetics of OS and highlighted the clinical benefits in the field of OS research [35]. Morrow et al highlighted the genetic and epigenetic defects in OS and emphasized the role of epigenetic dysregulation in tumor suppression and oncogene regulation [6].…”

Section: Epigenetic Modification In Os Progressionmentioning

confidence: 99%

Deciphering the Signaling Mechanisms of Osteosarcoma Tumorigenesis

Nirala

Yamamichi

Yustein

2023

IJMS

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Osteosarcoma (OS) is the predominant primary bone tumor in the pediatric and adolescent populations. It has high metastatic potential, with the lungs being the most common site of metastasis. In contrast to many other sarcomas, OS lacks conserved translocations or genetic mutations; instead, it has heterogeneous abnormalities, including somatic DNA copy number alteration, ploidy, chromosomal amplification, and chromosomal loss and gain. Unfortunately, clinical outcomes have not significantly improved in over 30 years. Currently, no effective molecularly targeted therapies are available for this disease. Several genomic studies showed inactivation in the tumor suppressor genes, including p53, RB, and ATRX, and hyperactivation of the tumor promoter genes, including MYC and MDM2, in OS. Alterations in the major signaling pathways, including the PI3K/AKT/mTOR, JAK/STAT, Wnt/β-catenin, NOTCH, Hedgehog/Gli, TGF-β, RTKs, RANK/RANKL, and NF-κB signaling pathways, have been identified in OS development and metastasis. Although OS treatment is currently based on surgical excision and systematic multiagent therapies, several potential targeted therapies are in development. This review focuses on the major signaling pathways of OS, and we propose a biological rationale to consider novel and targeted therapies in the future.

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“…Twenhafel et. al has reviewed how epigenetic changes are associated with disease progression in osteosarcoma [67]. DNA methylation can suppress miRNAs, whose underexpression in osteosarcoma tissue is correlated with higher-stage tumors.…”

Section: Plos Onementioning

confidence: 99%

Asymmetric and symmetric protein arginine methylation in methionine-addicted human cancer cells

Holtz,

Lowe,

Aoki

et al. 2023

PLoS ONE

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The methionine addiction of cancer cells is known as the Hoffman effect. While non-cancer cells in culture can utilize homocysteine in place of methionine for cellular growth, most cancer cells require exogenous methionine for proliferation. It has been suggested that a biochemical basis of this effect is the increased utilization of methionine for S-adenosylmethionine, the major methyl donor for a variety of cellular methyltransferases. Recent studies have pointed to the role of S-adenosylmethionine-dependent protein arginine methyltransferases (PRMTs) in cell proliferation and cancer. To further understand the biochemical basis of the methionine addiction of cancer cells, we compared protein arginine methylation in two previously described isogenic cell lines, a methionine-addicted 143B human osteosarcoma cell line and its less methionine-dependent revertant. Previous work showed that the revertant cells were significantly less malignant than the parental cells. In the present study, we utilized antibodies to detect the asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) products of PRMTs in polypeptides from cellular extracts and purified histone preparations of these cell lines fractionated by SDS-PAGE. Importantly, we observed little to no differences in the banding patterns of ADMA- and SDMA-containing species between the osteosarcoma parental and revertant cell lines. Furthermore, enzymatic activity assays using S-adenosyl-ʟ-[methyl-3H] methionine, recombinantly purified PRMT enzymes, cell lysates, and specific PRMT inhibitors revealed no major differences in radiolabeled polypeptides on SDS-PAGE gels. Taken together, these results suggest that changes in protein arginine methylation may not be major contributors to the Hoffman effect and that other consequences of methionine addiction may be more important in the metastasis and malignancy of osteosarcoma and potentially other cancers.

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Epigenetic Changes Associated with Osteosarcoma: A Comprehensive Review

Cited by 9 publications

References 87 publications

Osteosarcoma in a ceRNET perspective

Osteosarcoma in a ceRNET perspective

Deciphering the Signaling Mechanisms of Osteosarcoma Tumorigenesis

Asymmetric and symmetric protein arginine methylation in methionine-addicted human cancer cells

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