Discover oncology · 2026
Cancer-associated adipocytes promote breast cancer progression by upregulating miR-106b-3p to target SLK.
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Zhou Xiaomei, Xiao Jun, Yang Zihui, Zeng Ning, Wu Haibin, Zhang Jun, Wu Yiping
Аннотация
PURPOSE: Adipocytes are the most abundant primary stromal cells in breast cancer (BC). Cancer-associated adipocytes (CAAs) driven by cancer cells are considered important regulators in the BC tumor microenvironment. However, the specific mechanism underlying the interplay of CAAs and BC cells remains unclear.
METHODS: We obtained CAAs by co-culturing adipocytes and MDA-MB-231 cells. RNA sequencing of MDA-MB-231 cells cultured in CAA-conditioned medium (CAA-CM) identified miR-106b-3p. We down-regulated miR-106b-3p expression in BC cells and assessed proliferation, migration, and invasion in vitro. In allograft and lung metastasis mouse models, we tested whether the tumor-promoting effects of CAA-CM could be counteracted by a miR-106b-3p inhibitor. Dual-luciferase assay and rescuing assay were used to reveal the functional target.
RESULTS: CAAs exhibited a fibroblast-like appearance with reduced lipid droplets and decreased expression of mature adipocyte markers. miR-106b-3p was selected as a candidate miRNA from exploratory profiling and was further validated as a contributor to CAA-CM-associated malignant phenotypes in BC cells. Silencing miR-106b-3p suppressed BC cell proliferation, migration, and invasion in vitro. In allograft and lung metastasis models, the tumor-promoting effects of CAA-CM were counteracted by a miR-106b-3p inhibitor. Ste20-like kinase (SLK) was confirmed as the functional target of miR-106b-3p.
CONCLUSION: We confirmed that CAAs promoted the proliferation, migration, invasion, and in vivo lung metastasis of BC cells by upregulating miR-106b-3p, which targeted and inhibited SLK expression. These effects were accompanied by increased PI3K/AKT phosphorylation, suggesting a potential association between the miR-106b-3p/SLK axis and PI3K/AKT pathway activation.
METHODS: We obtained CAAs by co-culturing adipocytes and MDA-MB-231 cells. RNA sequencing of MDA-MB-231 cells cultured in CAA-conditioned medium (CAA-CM) identified miR-106b-3p. We down-regulated miR-106b-3p expression in BC cells and assessed proliferation, migration, and invasion in vitro. In allograft and lung metastasis mouse models, we tested whether the tumor-promoting effects of CAA-CM could be counteracted by a miR-106b-3p inhibitor. Dual-luciferase assay and rescuing assay were used to reveal the functional target.
RESULTS: CAAs exhibited a fibroblast-like appearance with reduced lipid droplets and decreased expression of mature adipocyte markers. miR-106b-3p was selected as a candidate miRNA from exploratory profiling and was further validated as a contributor to CAA-CM-associated malignant phenotypes in BC cells. Silencing miR-106b-3p suppressed BC cell proliferation, migration, and invasion in vitro. In allograft and lung metastasis models, the tumor-promoting effects of CAA-CM were counteracted by a miR-106b-3p inhibitor. Ste20-like kinase (SLK) was confirmed as the functional target of miR-106b-3p.
CONCLUSION: We confirmed that CAAs promoted the proliferation, migration, invasion, and in vivo lung metastasis of BC cells by upregulating miR-106b-3p, which targeted and inhibited SLK expression. These effects were accompanied by increased PI3K/AKT phosphorylation, suggesting a potential association between the miR-106b-3p/SLK axis and PI3K/AKT pathway activation.