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miR-221/222 promotes S-phase entry and cellular migration in control of basal-like breast cancer.

Molecules (Basel, Switzerland) | 2014

The miR-221/222 cluster has been demonstrated to function as oncomiR in human cancers. miR-221/222 promotes epithelial-to-mesenchymal transition (EMT) and confers tamoxifen resistance in breast cancer. However, the effects and mechanisms by which miR-221/222 regulates breast cancer aggressiveness remain unclear. Here we detected a much higher expression of miR-221/222 in highly invasive basal-like breast cancer (BLBC) cells than that in non-invasive luminal cells. A microRNA dataset from breast cancer patients indicated an elevated expression of miR-221/222 in BLBC subtype. S-phase entry of the cell cycle was associated with the induction of miR-221/222 expression. miRNA inhibitors specially targeting miR-221 or miR-222 both significantly suppressed cellular migration, invasion and G1/S transition of the cell cycle in BLBC cell types. Proteomic analysis demonstrated the down-regulation of two tumor suppressor genes, suppressor of cytokine signaling 1 (SOCS1) and cyclin-dependent kinase inhibit 1B (CDKN1B), by miR-221/222. This is the first report to reveal miR-221/222 regulation of G1/S transition of the cell cycle. These findings demonstrate that miR-221/222 contribute to the aggressiveness in control of BLBC.

Pubmed ID: 24886939 RIS Download

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Associated grants

  • Agency: NCI NIH HHS, United States
    Id: R01CA75503
  • Agency: NCI NIH HHS, United States
    Id: P30CA056036
  • Agency: NCI NIH HHS, United States
    Id: R01CA107382
  • Agency: NCI NIH HHS, United States
    Id: R01CA70896

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