MiR-106b expression determines the proliferation paradox of TGF-β in breast cancer cells

Abstract

TGF-β has paradoxical effects on cancer cell proliferation, as it suppresses proliferation of normal epithelial and low-invasive cancer cells, but enhances that of high-invasive cancer cells. However, how cancer cells acquire the ability to evade the tumor-suppressing effects of TGF-β, yet still take advantage of its tumor-promoting effects, remains elusive. Here, we identified miR-106b as a molecular switch to determine TGF-β effects on cell proliferation. TGF-β1 enhances the transcription of miR-106b via a promoter independent of its host gene MCM7 by activating c-jun. In high-invasive breast cancer cells, miR-106b is upregulated by TGF-β1 at a much higher level than that in normal or low-invasive cancer cells. Accumulation of miR-106b counterbalances TGF-β growth-inhibiting effects by eliminating activated retinoblastoma (RB) and results in enhanced proliferation. Furthermore, miR-106b mediates TGF-β effects on tumor growth and metastasis in breast cancer xenografts. In addition, miR-106b expression is elevated in higher stage tumors and correlated with tumor progression in breast cancer patients. These findings suggest that high level of miR-106b induced by TGF-β determines the tumor-promoting effects of TGF-β in breast cancer.

BRMS1L suppresses breast cancer metastasis by inducing epigenetic silence of FZD10

“…Inhibiting miR-106b by antisense oligonucleotides successfully restored BRMS1L expression and inhibits EMT in breast cancer cells. Our recent study and others have shown that miR-106b overexpression in breast cancers correlates with tumour metastasis and poor patient outcome 38,48 . Moreover, miR-106b is a potent oncomiR that has been shown to target and silence a list of tumour-suppressing genes, including Rb 49 , smad7 (ref.…”

miR-93 and PTEN: Key regulators of doxorubicin-resistance and EMT in breast cancer

“…miR-93, along with miR-106b and miR-25, is a member of the miR-106b-25 cluster, which is located in its host gene, MCM7 (24). All members of the miR-106b-25 cluster, in addition to MCM7, have been reported to be involved in tumorigenesis (25)(26)(27) and drug resistance (28,29) in multiple tumors. Furthermore, our previous study on miRNA profiles revealed that miR-93 was the most upregulated miRNA of this cluster in the doxorubicin-resistant MCF-7 cells compared with the parental MCF-7 cells, which indicated that miR-93 may be the major contributor to the drug resistance of breast cancer cells in this cluster.…”

The microRNA-205-5p is correlated to metastatic potential of 21T series: A breast cancer progression model

“…miR-3934 predicted targets include components of the oncogenic Wnt signaling pathway such as WNT7, WNT9A, MAPK10, APC and ROCK2 [17]. The up-regulated miRNAs in all 21T cell lines, suggesting an early event in tumorigenesis include the oncomiRs miR-29a/b/c [18, 19], miR-141 [20, 21], miR106b [22] and miR-96 [23, 24]. In this study, we focus our attention at the miRNA profile during the progression from an in situ tumor to a metastatic phenotype.…”