During the female lifetime, the expansion of the epithelium dictated by the ovarian cycles is supported by a transient increase in the mammary epithelial stem cell population (MaSCs). Notably, activation of Wnt/β-catenin signaling is an important trigger for MaSC expansion. Here, we report that the miR-424/503 cluster is a modulator of canonical Wnt signaling in the mammary epithelium. We show that mammary tumors of miR-424(322)/503-depleted mice exhibit activated Wnt/β-catenin signaling. Importantly, we show a strong association between miR-424/503 deletion and breast cancers with high levels of Wnt/β-catenin signaling. Moreover, miR-424/503 cluster is required for Wnt-mediated MaSC expansion induced by the ovarian cycles. Lastly, we show that miR-424/503 exerts its function by targeting two binding sites at the 3'UTR of the LRP6 co-receptor and reducing its expression. These results unveil an unknown link between the miR-424/503, regulation of Wnt signaling, MaSC fate, and tumorigenesis.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8647148PMC
http://dx.doi.org/10.15252/embr.202153201DOI Listing

Publication Analysis

Top Keywords

wnt/β-catenin signaling
16
signaling mammary
8
mammary epithelium
8
ovarian cycles
8
masc expansion
8
mir-424/503 cluster
8
wnt signaling
8
mir-424/503
6
signaling
6
mir-424/503 modulates
4

Similar Publications

First-line immune checkpoint inhibitor (ICI) combinations show responses in subsets of hepatocellular carcinoma (HCC) patients. Nearly half of HCCs are Wnt-active with mutations in (encoding for β-catenin), , or , and demonstrate limited benefit to ICI due to an immune excluded tumor microenvironment. We show significant tumor responses in multiple β-catenin-mutated immunocompetent HCC models to a novel siRNA encapsulated in lipid nanoparticle targeting (LNP-CTNNB1).

View Article and Find Full Text PDF

The potential role of chromodomain helicase DNA-binding protein 3 in defining the cervical width by regulating the early growth stage of the apical papilla during tooth development.

J Oral Biosci

December 2024

Division of Anatomical and Cellular Pathology, Department of Pathology, Iwate Medical University, 1-1-1 Idaidori, Yahaba-cho, Shiwa-gun, Iwate, 028-3694, Japan. Electronic address:

Objective: This study aimed to evaluate the role of the chromodomain helicase DNA-binding protein 3 (CHD3) in tooth morphogenesis in Chd3 knockout mice.

Methods: Chd3 knockout mice were generated using the CRISPR-Cas9 method. Mandibular first molars were extracted from the mice and their littermates and morphometrically analyzed.

View Article and Find Full Text PDF

Background: Diabetes mellitus (DM) is a prevalent chronic disease that is becoming increasingly common worldwide and can lead to a number of dangerous complications. The Wnt signaling pathway is important for the onset and progression of diabetes. Wnt3a is a typical Wnt ligand that can increase the stability of β-catenin, control TCF7L2 expression, promote β-cell proliferation, and reduce apoptosis.

View Article and Find Full Text PDF

Background: Adipose mesenchymal stem cells (ADSCs) exert beneficial effects on kidney disease through a paracrine mechanism. However, the specific molecular mechanisms by which ADSCs treat renal fibrosis are not yet fully understood. Therefore, it is crucial to clarify the therapeutic effects of ADSC-derived extracellular vesicles (ADSC-EVs) on the progression of renal fibrosis and their underlying mechanisms.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!