Enhancer Extrachromosomal Circular DNA ANKRD28 Elicits Drug Resistance via POU2F2-Mediated Transcriptional Network in Multiple Myeloma.

ABSTRACT: Multiple myeloma (MM) remains an incurable disease primarily due to the emergence of drug resistance, and the underlying mechanisms remain unclear. Extrachromosomal circular DNAs (eccDNAs) are prevalent in cancer genomes of both coding and non-coding regions. However, the role of non-coding eccDNA regions that serve as enhancers has been largely overlooked. Here, genome-wide profiling of serum eccDNAs from donors and MM patients who responded well or poorly to bortezomib-lenalidomide-dexamethasone (VRd) therapy is characterized. A high copy number of eccDNA ANKRD28 (eccANKRD28) predicts poor therapy response and prognosis but enhanced transcriptional activity. Established VRd-resistant MM cell lines exhibit a higher abundance of eccANKRD28, and CRISPR/Cas9-mediated elevation of eccANKRD28

SUBMITTER: Chen B 

PROVIDER: S-EPMC12140331 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature