The Landscape of Regulatory Noncoding RNAs in Ewing’s Sarcoma

Barrett, Connor; Budhiraja, Anuj; Parashar, Vijay; Batish, Mona

doi:10.3390/biomedicines9080933

Cited by 9 publications

(8 citation statements)

References 108 publications

(111 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similar activity of the IL-1β/NF-κB signaling pathway involving the NF-κB/miR-181α-5p/RASSF1A/Wnt-β-catenin pathway can also be hypothesized in other pediatric solid tumors, including EWS [39][40][41]. The role of IL-1β and Wnt signaling has also been implicated in the bone metastatic growth of breast cancer [21], which will be discussed in the section dedicated to the IL-1 family in bone metastasis.…”

Section: Il-1 Family In Osteosarcomamentioning

confidence: 80%

IL-1 Family Members in Bone Sarcomas

Landuzzi,

Ruzzi,

Pellegrini

et al. 2024

Cells

View full text Add to dashboard Cite

IL-1 family members have multiple pleiotropic functions affecting various tissues and cells, including the regulation of the immune response, hematopoietic homeostasis, bone remodeling, neuronal physiology, and synaptic plasticity. Many of these activities are involved in various pathological processes and immunological disorders, including tumor initiation and progression. Indeed, IL-1 family members have been described to contribute to shaping the tumor microenvironment (TME), determining immune evasion and drug resistance, and to sustain tumor aggressiveness and metastasis. This review addresses the role of IL-1 family members in bone sarcomas, particularly the highly metastatic osteosarcoma (OS) and Ewing sarcoma (EWS), and discusses the IL-1-family-related mechanisms that play a role in bone metastasis development. We also consider the therapeutic implications of targeting IL-1 family members, which have been proposed as (i) relevant targets for anti-tumor and anti-metastatic drugs; (ii) immune checkpoints for immune suppression; and (iii) potential antigens for immunotherapy.

show abstract

Section: Il-1 Family In Osteosarcomamentioning

confidence: 80%

IL-1 Family Members in Bone Sarcomas

Landuzzi,

Ruzzi,

Pellegrini

et al. 2024

Cells

View full text Add to dashboard Cite

show abstract

“…The ceRNA networks centered on FLI1 have rarely been reported, and most have been characterized in Ewing sarcoma. Several miRNAs, such as let-7g, miR-22, miR-30a-5p and miR-145, are closely related to EWS-FLI1 regulation [ 49 , 50 ]. A ceRNA network targeting FLI1 has also reported in other types of cancers, including the miR-33b/FLI1 axis in hepatocellular carcinoma and the miR-145/FLI1 axis in colon cancer [ 51 , 52 ].…”

Section: Discussionmentioning

confidence: 99%

Integrated analysis reveals FLI1 regulates the tumor immune microenvironment via its cell-type-specific expression and transcriptional regulation of distinct target genes of immune cells in breast cancer

Pei,

Peng,

et al. 2024

BMC Genomics

View full text Add to dashboard Cite

Background Immunotherapy is a practical therapeutic approach in breast cancer (BRCA), and the role of FLI1 in immune regulation has gradually been unveiled. However, the specific role of FLI1 in BRCA was conflicted; thus, additional convincing evidence is needed. Methods We explored the upstream regulation of FLI1 expression via summary data-based Mendelian randomization (SMR) analysis and ncRNA network construction centering on FLI1 using BRCA genome-wide association study (GWAS) summary data with expression quantitative trait loci (eQTLs) and DNA methylation quantitative trait loci (mQTLs) from the blood and a series of in silico analyses, respectively. We illuminated the downstream function of FLI1 in immune regulation by integrating a series of analyses of single-cell RNA sequence data (scRNA-seq). Results We verified a causal pathway from FLI1 methylation to FLI1 gene expression to BRCA onset and demonstrated that FLI1 was downregulated in BRCA. FLI1, a transcription factor, served as myeloid and T cells’ communication regulator by targeting immune-related ligands and receptor transcription in BRCA tissues. We constructed a ceRNA network centering on FLI1 that consisted of three LncRNAs (CKMT2-AS1, PSMA3-AS1, and DIO3OS) and a miRNA (hsa-miR-324-5p), and the expression of FLI1 was positively related to a series of immune-related markers, including immune cell infiltration, biomarkers of immune cells, and immune checkpoints. Conclusion Low-methylation-induced or ncRNA-mediated downregulation of FLI1 is associated with poor prognosis, and FLI1 might regulate the tumor immune microenvironment via a cell-type-specific target genes manner in BRCA.

show abstract

“…Non-coding RNAs (ncRNAs), including miRNAs and lncRNAs, are key regulators of transcription, translation, and signaling pathways. There is evidence that these ncRNAs are important epigenetic and transcriptional regulators of Ewing sarcoma oncogenesis ( 61 , 62 ). In addition, while EWS::FLI1 can modulate ncRNA expression, the fusion may in turn be regulated by these transcripts ( 48 , 63 ).…”

Section: Cell Autonomous Regulators Of Ews::fli1 Transcript Expressionmentioning

confidence: 99%

The importance of fusion protein activity in Ewing sarcoma and the cell intrinsic and extrinsic factors that regulate it: A review

2022

View full text Add to dashboard Cite

Accumulating evidence shows that despite clonal origins tumors eventually become complex communities comprised of phenotypically distinct cell subpopulations. This heterogeneity arises from both tumor cell intrinsic programs and signals from spatially and temporally dynamic microenvironments. While pediatric cancers usually lack the mutational burden of adult cancers, they still exhibit high levels of cellular heterogeneity that are largely mediated by epigenetic mechanisms. Ewing sarcomas are aggressive bone and soft tissue malignancies with peak incidence in adolescence and the prognosis for patients with relapsed and metastatic disease is dismal. Ewing sarcomas are driven by a single pathognomonic fusion between a FET protein and an ETS family transcription factor, the most common of which is EWS::FLI1. Despite sharing a single driver mutation, Ewing sarcoma cells demonstrate a high degree of transcriptional heterogeneity both between and within tumors. Recent studies have identified differential fusion protein activity as a key source of this heterogeneity which leads to profoundly different cellular phenotypes. Paradoxically, increased invasive and metastatic potential is associated with lower EWS::FLI1 activity. Here, we review what is currently understood about EWS::FLI1 activity, the cell autonomous and tumor microenvironmental factors that regulate it, and the downstream consequences of these activity states on tumor progression. We specifically highlight how transcription factor regulation, signaling pathway modulation, and the extracellular matrix intersect to create a complex network of tumor cell phenotypes. We propose that elucidation of the mechanisms by which these essential elements interact will enable the development of novel therapeutic approaches that are designed to target this complexity and ultimately improve patient outcomes.

show abstract

The Landscape of Regulatory Noncoding RNAs in Ewing’s Sarcoma

Cited by 9 publications

References 108 publications

IL-1 Family Members in Bone Sarcomas

IL-1 Family Members in Bone Sarcomas

Integrated analysis reveals FLI1 regulates the tumor immune microenvironment via its cell-type-specific expression and transcriptional regulation of distinct target genes of immune cells in breast cancer

The importance of fusion protein activity in Ewing sarcoma and the cell intrinsic and extrinsic factors that regulate it: A review

Contact Info

Product

Resources

About