Oral Presentation 14th International Biennial Conference on Metastasis Research 2012

MiR-106b is regulated by transforming growth factor β signaling and promotes metastasis in breast cancer (#17)

Chang Gong 1 , Shaohua Qu 1 , Shujuan Pan 1 , Yu Jiao 1 , Bodu Liu 1 , Erwei Song 1
  1. Sun-Yat-Sen Memorial Hospital, Sun-Yat-Sen University, Guangzhou, GD, China

Exposure of tumor cells to Transforming Growth Factor β (TGF-β) induces epithelial-mesenchymal transition (EMT) and generates cells with a stable cancer stem cell (CSC) phenotype, which promotes metastasis in advanced malignancy. TGF-β promotes EMT by a combination of Smad-dependent transcriptional events and Smad-independent effects. A role for the microRNA (miRNA) in TGF-β/Smad signaling has recently been appreciated. However, the role of microRNAs in the noncanonical TGF-βsignalings remains illusive. Our previous study found that breast CSCs had elevated miR-106b, a member of miR-106b family,thus, the role of miR-106b in TGF-βinduced EMT was further investigated. Here, we profiled that miRNA signature of EMT induced by TGF-βin normal human mammary gland epitherial cells. We further demonstrated that TGF-β1 transcriptionally upregulates miR-106b via c-jun. miR-106b mediates TGF-β-induced proliferation, EMT, migration and invasion as well as self-renew. Morever, breast cancer metastasis-suppressor 1-like (BRMS1L) and Retinoblastoma1(RB1) are negatively regulated by miR-106b and contribute to TGF-β-induced phenotypes. In addition, oncogeneic function of miR-106b was also validated in mouse models and clinical correlation studies.