Transcriptional regulation of KCNA2 coding Kv1.2 by EWS::FLI1: involvement in controlling the YAP/Hippo signalling pathway and cell proliferation DOI Creative Commons

Maryne Dupuy,

Anaïs Postec,

Mathilde Mullard

et al.

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: Dec. 18, 2024

Ewing sarcoma (ES), the second main pediatric bone sarcoma, is characterised by a chromosomal translocation leading to formation of fusion proteins like EWS::FLI1. While several studies have shown that potassium channels drive development many tumours, limited data exist on ES. This work therefore aimed study transcriptional regulation KCNA2 and define involvement Kv1.2 channel encoded in key function ES development, cell proliferation. expression patients lines was measured via bioinformatic analysis (RNA-Seq). The presence functional using patch-clamp experiments. Molecular biology approaches were used after EWS::FLI1 silencing KCNA2. Proliferation count assessment performed approaches. (siRNA) RNA-Seq identify signalling pathways involved ability Hippo pathway studied measuring Hippo/YAP target genes expression, while YAP protein with Western-Blot immunofluorescence research identified (encoding for channel) as highly expressed biopsies lines. results indicated correlation between patient survival. also demonstrated KCNA2/Kv1.2 direct EWS::FLI1, molecular mechanisms which this chimeric regulates gene at level. Furthermore, activity regulate proliferation drives pathway. Using specific inhibitor (κ-Conotoxin), suggested two complementary are process, both dependently independently plasma membrane. first describe cancer development. unveiled cascade. Thus, suggests could be potential therapeutic

Language: Английский

Superficial Neurocristic EWSR1::FLI1 Fusion Tumor: A Distinctive, Clinically Indolent, S100 Protein/SOX10-Positive Neoplasm DOI
Andrew L. Folpe, Michael T. Tetzlaff,

Steven D Billings

et al.

Modern Pathology, Journal Year: 2024, Volume and Issue: 37(8), P. 100537 - 100537

Published: June 12, 2024

Language: Английский

Citations

6
Novel classification system and high-risk categories of pediatric acute myeloid leukemia DOI Creative Commons

Masayuki Umeda,

Yen‐Chun Liu, Seth E. Karol

et al.

Haematologica, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 9, 2025

The prognosis of pediatric acute myeloid leukemia (AML) remains poor compared with lymphoblastic (ALL); accurate diagnosis and treatment strategies based on the genomic background are strongly needed. Recent advances in sequencing technologies have identified novel AML subtypes, including BCL11B structural variants UBTF tandem duplications (UBTF-TD), associated prognosis. In contrast, these subtypes do not fit into diagnostic systems for 5th edition WHO classification or International Consensus Classifications (ICC) released 2022. this review, we describe current state context a new framework findings updated profiling. Molecular categories system unique transcriptional, mutational, clinical characteristics, which can be leveraged predicting outcomes developing molecular-target therapies initiating driver alterations. We also highlight four high-risk AML, namely CBFA2T3::GLIS2, BCL11B, UBTF-TD, ETS family fusions, focusing their disease mechanisms, associations, possible therapeutic to overcome dismal

Language: Английский

Citations

0
Perinatal exposure to ambient fine particle air pollution and risk of childhood ewing sarcoma in a population-based case-control study in California (1988–2015) DOI Creative Commons
Cassandra J. Clark, Rong Wang, Joseph L. Wiemels

et al.

Environmental Health, Journal Year: 2025, Volume and Issue: 24(1)

Published: March 7, 2025

Abstract Background Incidence of childhood Ewing sarcoma, a rare cancer affecting bones and soft tissues, is increasing. Environmental exposures during the perinatal period, like air pollution, may play role. We examined exposure to ambient fine particulate matter (PM 2.5 ) sarcoma risk in case-control linkage study nested within California birth cohort. Methods The included 388 children born (1982–2015) diagnosed with at age 0–19 years (1988–2015), 19,341 California-born cancer-free controls frequency-matched cases on year (50:1 ratio). Ambient PM concentrations maternal residence were averaged separately over two time periods, gestation first after birth, using validated ensemble-based model (categorized as quartiles). estimated odds ratios (ORs) 95% confidence intervals (CIs) for association between risk, adjusting sex, year, race, ethnicity, weight, education stratifying by Hispanic ethnicity assess potential disparities -related risk. Results In overall population, was not associated when considering or birth. Among children, who experienced greater pollution compared non-Hispanic higher levels yielded elevated quartile (Q2 OR [95% CI] = 1.53 [0.94–2.51]; Q3 1.56 [0.95–2.56]; Q4 1.39 [0.79–2.47]). also relation Conclusion Our results provide new suggestive evidence that contribute although these findings statistically significant specific children. These require replication underscore need further evaluate role -cancer relationship genetic ancestry measures through lens environmental justice.

Language: Английский

Citations

0
The RNA tether model for human chromosomal translocation fragile zones DOI
D Liu, Chih‐Lin Hsieh, Michael R. Lieber

et al.

Trends in Biochemical Sciences, Journal Year: 2024, Volume and Issue: 49(5), P. 391 - 400

Published: March 14, 2024

Language: Английский

Citations

3
Preclinical models for the study of pediatric solid tumors: focus on bone sarcomas DOI Creative Commons
D. Isabel Petrescu, Jason T. Yustein, Atreyi Dasgupta

et al.

Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14

Published: July 18, 2024

Sarcomas comprise between 10–15% of all pediatric malignancies. Osteosarcoma and Ewing sarcoma are the two most common bone tumors diagnosed in children young adults. These commonly treated with surgery and/or radiation therapy combination chemotherapy. However, there is a strong need for development utilization targeted therapeutic methods to improve patient outcomes. Towards accomplishing this goal, pre-clinical models these unique malignancies particular importance design test experimental strategies prior being introduced patients due their origination site propensity metastasize. Pre-clinical offer several advantages study sarcomas benefits shortcomings dependent on type model. This review addresses types available solid tumors, special attention osteosarcoma sarcoma.

Language: Английский

Citations

2
Signaling pathways and targeted therapies in Ewing sarcoma DOI Creative Commons
Jia Ke, Li Cao, Yihan Yu

et al.

Pharmacology & Therapeutics, Journal Year: 2024, Volume and Issue: 266, P. 108765 - 108765

Published: Nov. 30, 2024

Language: Английский

Citations

2
Bioinformatics Analysis of the Biological Properties of Ewing Sarcoma DOI Open Access

Luchang Chen,

Huifang Zeng,

Wujia Yang

et al.

Journal of Biosciences and Medicines, Journal Year: 2024, Volume and Issue: 12(06), P. 202 - 215

Published: Jan. 1, 2024

Language: Английский

Citations

0
Unlocking epigenetics for precision treatment of Ewing's sarcoma. DOI
Zhehao Fan,

Shuangshuang Dong,

Ning Wang

et al.

PubMed, Journal Year: 2024, Volume and Issue: 36(3), P. 322 - 340

Published: June 30, 2024

Ewing's sarcoma (EWS) is a highly aggressive malignant bone tumor primarily affecting adolescents and young adults. Despite the efficacy of chemoradiotherapy in some cases, cure rate for patients with metastatic recurrent disease remains low. Therefore, there an urgent need innovative therapeutic approaches to address challenges associated EWS treatment. Epigenetic regulation, crucial factor physiological processes, plays significant role controlling cell proliferation, maintaining gene integrity, regulating transcription. Recent studies highlight importance abnormal epigenetic regulation initiation progression EWS. A comprehensive understanding intricate interactions between aberrant essential advancing clinical drug development. This review aims provide overview both targets implicated EWS, integrating various modalities offer perspectives diagnosis treatment

Language: Английский

Citations

0
Bioinformatics Analysis of the Association between Ewing’s Sarcoma and Tuberculosis Comorbidity DOI Open Access
Jun Huang, Lu Qi,

Junxiu Zhou

et al.

Journal of Biosciences and Medicines, Journal Year: 2024, Volume and Issue: 12(08), P. 128 - 140

Published: Jan. 1, 2024

Language: Английский

Citations

0
Transcriptional regulation of KCNA2 coding Kv1.2 by EWS::FLI1: involvement in controlling the YAP/Hippo signalling pathway and cell proliferation DOI Creative Commons

Maryne Dupuy,

Anaïs Postec,

Mathilde Mullard

et al.

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: Dec. 18, 2024

Ewing sarcoma (ES), the second main pediatric bone sarcoma, is characterised by a chromosomal translocation leading to formation of fusion proteins like EWS::FLI1. While several studies have shown that potassium channels drive development many tumours, limited data exist on ES. This work therefore aimed study transcriptional regulation KCNA2 and define involvement Kv1.2 channel encoded in key function ES development, cell proliferation. expression patients lines was measured via bioinformatic analysis (RNA-Seq). The presence functional using patch-clamp experiments. Molecular biology approaches were used after EWS::FLI1 silencing KCNA2. Proliferation count assessment performed approaches. (siRNA) RNA-Seq identify signalling pathways involved ability Hippo pathway studied measuring Hippo/YAP target genes expression, while YAP protein with Western-Blot immunofluorescence research identified (encoding for channel) as highly expressed biopsies lines. results indicated correlation between patient survival. also demonstrated KCNA2/Kv1.2 direct EWS::FLI1, molecular mechanisms which this chimeric regulates gene at level. Furthermore, activity regulate proliferation drives pathway. Using specific inhibitor (κ-Conotoxin), suggested two complementary are process, both dependently independently plasma membrane. first describe cancer development. unveiled cascade. Thus, suggests could be potential therapeutic

Language: Английский

Citations

0