Description
Triple-negative breast cancer (TNBC), an aggressive subtype of breast cancer with limited targeted therapeutics. By performing multiomic profiling, we revealed different super-enhancer (SE) patterns among various subtypes of breast cancer and one of TNBC-specific SEs specifically drives the expression of a novel oncogene TCOF1 (we name it TCOF1-SE). However, the exact upstream mechanisms that control TCOF1 expression by TCOF1-SE remain to be elucidated. Here, by combining DNA pull-down assay and bioinformatic prediction, we identified several potential transcription factors which bind to TCOF1-SE. FOSL1 was found to be one of the top genes in transcription factor DNA motif analysis. FOSL1 is often detected in the more aggressive and highly malignant subtypes of breast cancer, such as TNBC. Hence, the transcription factor FOSL1 was chosen for further study. FOSL1 depletion inhibits TCOF1 mRNA and protein levels. Furthermore, by performing dual-luciferase reporter assay and CHIP-qPCR, we demonstrated that FOSL1/TCOF1-SE interplay promotes the transcription of TCOF1 in TNBC cells. Moreover, FOSL1 knockdown inhibits the growth of TNBC cells in 2D and 3D spheroids, as well as supresses stemness properties. This work identifies TCOF1 as a direct transcriptional target of FOSL1, and highlights the potential of targeting FOSL1-SE-TCOF1 transcriptional program for therapeutic treatment of TNBC.| Period | 9 May 2023 |
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| Event title | BMS Research Gala 2023 |
| Event type | Conference |
| Location | HK, Hong KongShow on map |