The MYC-YBX1 Circuit in Maintaining Stem-like Vincristine-Resistant Cells in Rhabdomyosarcoma
Abstract
Rhabdomyosarcoma (RMS) is a pediatric soft tissue sarcoma that causes significant devastation, with no effective therapy for relapsed disease. The mechanisms behind treatment failures are poorly understood. Our study showed that treatment of RMS cells with vincristine led to an increase in CD133-positive stem-like resistant cells. Single cell RNAseq analysis revealed that MYC and YBX1 were among the top-scoring transcription factors in CD133-high expressing cells. Targeting MYC and YBX1 using CRISPR/Cas9 reduced stem-like characteristics and viability of the vincristine-resistant cells. MYC and YBX1 showed mutual regulation, with MYC binding to the YBX1 promoter and YBX1 binding to MYC mRNA. The MYC inhibitor MYC361i synergized with vincristine to reduce tumor growth and stem-like cells in a zebrafish model of RMS. MYC and YBX expression showed a positive correlation in RMS patients, and high MYC expression correlated with poor survival. Targeting the MYC-YBX1 axis holds promise for improving survival in RMS patients.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- May 17, 2023
- Source ID
- 10.3390/cancers15102788
Entities
People
- Eleanor Chen
- Kenian Chen
- Lin Xu
- Madeline Fritzke
- Spencer Stinson
- Thao Pham
- Weiliang Tang
- Yadong Wang
Organizations
- Cancer Prevention and Research Institute of Texas
- National Institutes of Health
- United States Department of Defense
- University of Texas Southwestern Medical Center
- University of Washington