Details

Autor(en) / Beteiligte

• Wang, Wenrui
• Zhang, Lingyu
• Wang, Yangyang
• Ding, Yongxing
• Chen, Tiantian
• Wang, Yueyue
• Wang, Haifeng
• Li, Yu
• Duan, Kecai
• Chen, Sulian
• Yang, Qingling
• Chen, Changjie

Titel

Involvement of miR-451 in resistance to paclitaxel by regulating YWHAZ in breast cancer

Ist Teil von

• Cell death & disease, 2017-10, Vol.8 (10), p.e3071-e3071

Ort / Verlag

England: Springer Nature B.V

Erscheinungsjahr

2017

Quelle

MEDLINE

Beschreibungen/Notizen

• MicroRNAs (miRNAs) have been identified as major post-transcriptional regulators of the initiation and progression of human cancers, including breast cancer. However, the detail role of miR-451 has not been fully elucidated in breast cancer. In this study, we aimed to investigate the biological role and molecular mechanisms of miR-451 in drug resistance in breast cancer cell lines and in xenograft model. We show that miR-451 is decreased in human breast cancer specimens and in paclitaxel-resistant (PR) cells. Ectopic expression of miR-451 could inhibit the cell migration and invasion, promoted apoptosis, induced cell-cycle arrest Furthermore, tyrosine3-monooxygenase/tryptophan5-monooxygenase activation protein zeta (YWHAZ) was identified as a direct target of miR-451. Remarkably, the expression of YWHAZ is inversely correlated with the level of miR-451 in human breast cancer samples. Co-treatment with miR-451 mimics and YWHAZ-siRNA significantly enhanced YWHAZ knockdown in both SKBR3/PR and MCF-7/PR cells Moreover, miR-451 markedly inhibited expression of β-catenin via YWHAZ and subsequently inhibited downstream gene cyclin D1, c-Myc expression. The results of xenograft model in vivo showed that intratumor injection of miR-451 agomir induced a tumor-suppressive effect in SKBR3/PR drug-resistant xenograft model. Taken together, our findings suggested that miR-451 might be considered as important and potential target in paclitaxel-resistant breast cancer treatment.