Scholarlink

Purpose <p>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.</p> Methods <p>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 <i>miR-106b-3p</i>. We down-regulated <i>miR-106b-3p</i> 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 <i>miR-106b-3p</i> inhibitor. Dual-luciferase assay and rescuing assay were used to reveal the functional target.</p> Results <p>CAAs exhibited a fibroblast-like appearance with reduced lipid droplets and decreased expression of mature adipocyte markers. <i>miR-106b-3p</i> 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 <i>miR-106b-3p</i> 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 <i>miR-106b-3p</i> inhibitor. Ste20-like kinase (<i>SLK</i>) was confirmed as the functional target of <i>miR-106b-3p</i>.</p> Conclusion <p>We confirmed that CAAs promoted the proliferation, migration, invasion, and in vivo lung metastasis of BC cells by upregulating <i>miR-106b-3p</i>, which targeted and inhibited <i>SLK</i> expression. These effects were accompanied by increased PI3K/AKT phosphorylation, suggesting a potential association between the <i>miR-106b-3p</i>/<i>SLK</i> axis and PI3K/AKT pathway activation.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Cancer-associated adipocytes promote breast cancer progression by upregulating miR-106b-3p to target SLK

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月10日

查看全文
  • Xiaomei Zhou,
  • Jun Xiao,
  • Zihui Yang,
  • Ning Zeng,
  • Haibin Wu,
  • Jun Zhang,
  • Yiping Wu

摘要

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.