The Regulation and Function of miR-21-FOXO3a-miR-34b/c Signaling in Breast Cancer

International Journal of Molecular Sciences

Lili Tang¹  Shaihong Zhu²  Liqiu Liao²  Xiangyan Liu²  Jie Feng³  Qing Xu⁴ 

[1] Department of Breast Surgery, the Xiangya Hospital, Central South University,138 Tongzipo Road, Changsha 410013, China;Department of General Surgery, the Xiangya Hospital, Central South University,138 Tongzipo Road, Changsha 410013, China;Department of Nursing, Thomas Jefferson University, Philadelphia, PA 19107, USA;Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA;

关键词: miR-21;    miR-34b/c;    FOXO3a;    breast cancer;    miRNAs injection;   

DOI  :  10.3390/ijms16023148

来源: DOAJ

【 摘 要 】

Upregulation of miR-21 (microRNA-21) and downregulation of miR-34b/c have been found in breast cancer (BC). However, their regulation mechanism and functionroles in BC have not been fully addressed. Here, we report that miR-21 levels wereinversely correlated with miR-34b/c levels in BC. MiR-21 upregulation contributes to PTEN downregulation, which is beneficial for the activation of PI3K/AKT signaling. The activation of AKT phosphorylates FOXO3a, triggering relocalization of FOXO3a proteins from the nucleus to the cytoplasm. FOXO3a is a newly identified transcription factor responsible for miR-34b/c expression. Downregulation of nuclear FOXO3a decreased the expression levels of miR-34b and miR-34c in breast cancer cells, in which p53 was mutated. We also found upregulation of circulating miR-21 and downregulation of circulating miR-34b/c in BC patients’ serum. More importantly, we showed that systemic delivery of miR-34b/c or with anti-miR-21 significantly inhibited breast tumor growth in vivo. These results suggest that high circulating levels of miR-21 and low levels of miR-34b/c may provide potential biomarkers for BC diagnosis, and systemic delivery of miR-34b/c has potential as a therapeutic option for BC treatment.

【 授权许可】

Unknown