RFX5 promotes the progression of triple-negative breast cancer through transcriptional activation of JAG1.

Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype characterized by high recurrence rates, low survival rates, and a lack of therapeutic targets. Regulatory Factor X5 (RFX5) is a critical transcription factor during tumor progression. However, the role of RFX5 involving breast cancer or TNBC has not been studied. This study obtained 60 tumor samples of TNBC for analysis and ascertained that RFX5 is linked with the severe stage. We constructed RFX5 knockdown and overexpression models involving TNBC cells. RFX5 overexpression enhanced TNBC cell proliferation by detecting cell vitality and replication of DNA and analyzing cell cycle data. RFX5 facilitated cell migration and invasion, which were determined by wound healing and Transwell assays. The anti-apoptotic RFX5 properties were confirmed with Hoechst staining and Annexin V/PI apoptosis assays. The Notch pathway was activated in TNBC, and Jagged canonical Notch ligand 1 (JAG1) could enhance TNBC growth and metastasis. RFX5 upregulation elevated JAG1 mRNA and protein levels. Chromatin immunoprecipitation and luciferase reporter assays indicated that RFX5 promoted the transcriptional activation of JAG1 by binding the promoter (- 1890/+ 15 or - 1359/+ 15 area). JAG1 knockdown reduced RFX5-induced expression of Notch signaling-related factors Notch1, NICD, and Hes1. This paper indicated that RFX5 is a transcription factor for JAG1 and established that RFX5 could activate the Notch pathway via transcriptional activation of JAG1 and promote TNBC progression. Targeting RFX5 could be a promising therapeutic approach against TNBC.