Send to

Choose Destination
Cell Death Dis. 2017 Oct 5;8(10):e3071. doi: 10.1038/cddis.2017.460.

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

Author information

Department of Biotechnology, Bengbu Medical College, Anhui 233030, China.
Clinical Testing and Diagnose Experimental Center, Bengbu Medical College, Anhui 233030, China.
Clinical Laboratory, The First People's Hospital of Changzhou, Jiangsu 213000, China.
Department of Oncology, Bengbu Central Hospital, Bengbu 233030, Anhui China.
Department of Biochemistry and Molecular Biology, Bengbu Medical College, Anhui 233030, China.


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.

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center