miR-181 elevates Akt signaling by co-targeting PHLPP2 and INPP4B phosphatases in luminal breast cancer.
Michaela StrotbekSimone SchmidIsmael Sánchez-GonzálezMelanie BoerriesHauke BuschMonilola A OlayioyePublished in: International journal of cancer (2017)
The PI3K-Akt pathway is one of the most commonly dysregulated cancer-associated signaling pathways. Here we report an oncogenic function for the miR-181 family in luminal breast cancer cells that involves Akt hyperactivation. We show that miR-181a and miR-181d posttranscriptionally suppress the expression of PHLPP2 and INPP4B phosphatases, resulting in elevated growth factor-induced Akt phosphorylation. Ectopic expression of miR-181a and miR-181d promoted S-phase entry and cell proliferation, which was reversed by pharmacological Akt inhibition. Importantly, the expression of miR-181 family members and PHLPP2/INPP2B are inversely correlated in primary human estrogen receptor-positive breast cancers, supporting the clinical relevance of our findings.
Keyphrases
- cell proliferation
- long non coding rna
- poor prognosis
- cell cycle
- long noncoding rna
- pi k akt
- growth factor
- signaling pathway
- estrogen receptor
- endothelial cells
- breast cancer cells
- oxidative stress
- young adults
- epithelial mesenchymal transition
- cancer therapy
- binding protein
- induced apoptosis
- high glucose
- breast cancer risk