MicroRNA-1 down-regulates proliferation and migration of breast cancer stem cells by inhibiting the Wnt/β-catenin pathway

Abstract

We investigated the miRNA profiles of breast cancer stem cells (CSCs) and non-CSC tumor cells by miRNA microarray and determined the effect of altered miR-1 expression on proliferation and migration of breast CSCs. The potential targets of miR-1 in the Wnt/β-catenin signaling were characterized by bioinformatics analysis and luciferase assay. We found that 14 miRNAs were up-regulated and 13 were down-regulated in the ESA+CD44+CD24−lineage− CSCs, related to ESA+CD44−CD24+lineage− non-CSC tumor cells. The miR-1 expression was associated inversely with aggressiveness of breast cancers. Furthermore, enhanced miR-1 expression decreased the percentages of SKBR3/CSCs and miR-1 inhibition increased the percentages of MCF-7/CSCs. Enhanced miR-1 expression significantly reduced the Frizzled 7 and Tankyrase-2 (TNKS2)-regulated luciferase activity in 293T cells and decreased Frizzled 7, TNKS2, c-Myc, octamer-binding transcription factor 4 (Oct4) and Nanog expression and the ratios of nuclear to cytoplasmic β-catenin as well as β-catenin-dependent luciferase activity in breast CSCs in vitro. miR-1 inhibited proliferation, migration and wound healing of breast CSCs in vitro. Enhanced miR-1 expression inhibited the growth of implanted MCF-7/CSCs while miR-1 inhibition promoted the growth of implanted MCF-7/CSCs in vivo. Our data indicate that miR-1 down-regulates breast CSC stemness, proliferation and migration by targeting the Frizzled 7 and TNKS2 to inhibit the Wnt/β-catenin signaling.

Overexpression of HACE1 in gastric cancer inhibits tumor aggressiveness by impeding cell proliferation and migration

“…The Wnt/ β ‐catenin signaling pathway played a crucial role in promoting cell proliferation and migration , and previous studies revealed that HECT domain‐containing E3 ligases were implicated in down‐regulation of Wnt/ β ‐catenin signaling . As one member of the HECT domain‐containing E3 ligases family, we postulated that HACE1 might inhibit cell proliferation and migration through down‐regulation of the Wnt/ β ‐catenin signaling pathway.…”

miR-150 Suppresses the Proliferation and Tumorigenicity of Leukemia Stem Cells by Targeting the Nanog Signaling Pathway

“…To further elucidate the molecular mechanism by which miR-150 regulates the proliferation of LSCs ( Figure 4A ), we tested the expression levels of genes including Notch2, Hsp90B1, and CTNNB1, besides Nanog (Zbinden et al, 2010; Liu et al, 2015; Zhu et al, 2015; White et al, 2016), which are known oncogenic and stem cell regulators that are implicated in leukemia initiation and progression. According to computational findings, they are targets of miR-150 ( Figure 6A ).…”

MicroRNA-137 inhibits BMP7 to enhance the epithelial-mesenchymal transition of breast cancer cells

“…Specifically, miRNAs have been shown to play an important role in the tumorigenesis of BC [20–28], and in the control of BMP7 activation [29–32]. However, previous studies on miR-137 never addressed BMP7 as a potential target [33–37].…”