{"id":"https://openalex.org/G801102498","display_name":"The Epigenome Analysis of the Mechanisms of Chemoresistance and Development new treatment in Rhabdoid Tumor","description":"Malignant rhabdoid tumor (MRT) is a highly aggressive pediatric cancer characterized by inactivation of SNF5, a core subunit of SWI/SNF complexes.\u3000Previously, we showed SNF5 contributes to transcriptional activation of NOXA, a pro-apoptotic protein that binds and inhibits the anti-apoptotic protein MCL-1. In this study, we found that NOXA expression was downregulated in both MRT cell lines and in clinical samples and that ectopically expressed NOXA bound MCL-1 and increased the sensitivity of MRT cell lines to doxorubicin (DOX) by promoting apoptosis. We also showed that knockdown of MCL-1 in MRT cell lines induced apoptosis and increased DOX sensitivity in MRT cells. Furthermore, we generate mice xenografts for both MCL-1 knockdown (KD) and control cell lines. We observed that mean tumor volume in the DOX-treated MCL-1 KD group was significantly smaller than that in the control group. Our results suggest that modulation of the NOXA/MCL-1 pathway underlies a chemoresistance in MRT.","funder_award_id":"25461602","funder":{"id":"https://openalex.org/F4320334764","display_name":"Japan Society for the Promotion of Science","doi":"10.13039/501100001691"},"funded_outputs":["https://openalex.org/W2137410693","https://openalex.org/W2205052393","https://openalex.org/W2341246595"],"funded_outputs_count":3,"parent_awards":[],"sub_awards":[],"sub_awards_count":0,"amount":5070000.0,"currency":"JPY","amount_usd":53711.72,"amount_usd_basis":"daily_rate","recipients":[],"recipient_countries":[],"recipient_regions":[],"research_scope":{"is_research":true,"basis":"funder_default","tier":1},"funding_type":"research","funder_scheme":"Grant-in-Aid for Scientific Research (C)","start_date":"2013-04-01","end_date":"2016-03-31","start_year":2013,"end_year":2016,"landing_page_url":"https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-25461602/","doi":null,"provenance":"kaken","lead_investigator":{"given_name":"YASUMICHI","family_name":"KUWAHARA","orcid":null,"role_start":null,"affiliation":{"name":"Kyoto Prefectural University of Medicine","country":"Japan","ids":[{"id":"https://nrid.nii.ac.jp/nrid/1000030590327","type":"nrid","asserted_by":"kaken"}]}},"co_lead_investigator":null,"investigators":null,"works_api_url":"https://api.openalex.org/works?filter=awards.id:G801102498","primary_topic":null,"topics":null,"institution_awarded":[{"id":"https://openalex.org/I40677808","display_name":"Kyoto Prefectural University of Medicine","ror":"https://ror.org/028vxwa22","country_code":"JP","type":"education","lineage":["https://openalex.org/I40677808","https://openalex.org/I4405285717"]}],"updated_date":"2026-10-23T03:01:05.000Z","created_date":"2026-07-13T04:17:19.000Z"}