MYBL1 is a super-enhancer-associated transcription factor that regulates cell proliferation in triple-negative breast cancer

Triple-negative breast cancer (TNBC) is an aggressive disease with few clinical therapeutic targets. Neoadjuvant chemotherapy before surgical intervention is nowadays the standard management for the disease, yet residual disease often includes drug-resistant persister cells with cancer stemness, which often generate tumor recurrence. Thus, the understanding of transcriptional regulatory network in TNBC cells will provide useful information to develop alternative targeted therapy for the disease. In the present study, we analyzed super-enhancers (SEs) that drive robust context-dependent transcriptional machinery in TNBC patient-derived and cultured cell models based on chromatin immunoprecipitation sequencing for acetyl histone H3K27. MYBL1 was identified as a top-ranked SE-associated transcription factor in TNBC cells. We showed that siRNA-mediated MYBL1 silencing repressed TNBC cell proliferation and migration. Transcriptomic analysis in TNBC cells revealed that MYBL1 silencing substantially downregulated genes involved in the cell cycle pathways. We demonstrated that MYBL1 and its target NCAPH are potential prognostic factors for patients with TNBC based on the immunohistochemisty of clinical TNBC tissues. Our findings reveal that MYBL1 plays an essential role in the transcriptional regulation in TNBC and can be a potential diagnostic and therapeutic target for the advanced disease.