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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

1
Department of Biotechnology, Bengbu Medical College, Anhui 233030, China.
2
Clinical Testing and Diagnose Experimental Center, Bengbu Medical College, Anhui 233030, China.
3
Clinical Laboratory, The First People's Hospital of Changzhou, Jiangsu 213000, China.
4
Department of Oncology, Bengbu Central Hospital, Bengbu 233030, Anhui China.
5
Department of Biochemistry and Molecular Biology, Bengbu Medical College, Anhui 233030, China.

Abstract

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.

PMID:
28981108
PMCID:
PMC5680582
DOI:
10.1038/cddis.2017.460
[Indexed for MEDLINE]
Free PMC Article

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