TGFB2-AS1 inhibits triple-negative breast cancer progression via interaction with SMARCA4 and regulating its targets TGFB2 and SOX2

Menée in vitro et à l'aide d'un modèle murin de cancer du sein triple négatif, cette étude met en évidence un mécanisme par lequel le long ARN non codant TGFB2-AS1, en interagissant avec la protéine SMARCA4 et en réprimant la transcription des gènes TGFB2 et SOX2, inhibe la progression tumorale

Résumé en anglais

Triple-negative breast cancer (TNBC) is the most challenging breast cancer subtype for its high rates of relapse, great metastatic potential, and short overall survival. How cancer cells acquire metastatic potency through the conversion of noncancer stem-like cells into cancer cells with stem-cell properties is poorly understood. Here, we identified the long noncoding RNA (lncRNA) TGFB2-AS1 as an important regulator of the reversibility and plasticity of noncancer stem cell populations in TNBC. We revealed that TGFB2-AS1 impairs the breast cancer stem-like cell (BCSC) traits of TNBC cells in vitro and dramatically decreases tumorigenic frequency and lung metastasis in vivo. Mechanistically, TGFB2-AS1 interacts with SMARCA4, a core subunit of the SWI/SNF chromatin remodeling complex, and results in transcriptional repression of its target genes including TGFB2 and SOX2 in an in cis or in trans way, leading to inhibition of transforming growth factor