miR-16-5p regulates apoptosis and migration of drug-resistant breast cancer cells by targeting YWHAQ.
10.12122/j.issn.1673-4254.2022.10.06
- Author:
Hai Tao ZHU
1
;
Hui Lan MAO
1
;
Shuang TAO
1
;
Wen Rui WANG
2
;
Chang Jie CHEN
3
;
Qing Ling YANG
3
Author Information
1. Anhui Provincial Key Laboratory of Cancer Translational Medicine, Bengbu Medical College, Bengbu 233000, China.
2. Department of Biotechnology, Bengbu Medical College, Bengbu 233000, China.
3. Department of Biochemistry and Molecular Biology, Bengbu Medical College, Bengbu 233000, China.
- Publication Type:Journal Article
- Keywords:
YWHAQ;
breast cancer;
drug resistance;
miR-16-5p
- MeSH:
Humans;
Female;
Breast Neoplasms/metabolism*;
bcl-2-Associated X Protein/metabolism*;
Cell Line, Tumor;
MicroRNAs/metabolism*;
Apoptosis;
Proto-Oncogene Proteins c-bcl-2/metabolism*;
Cell Movement;
Paclitaxel/pharmacology*;
Cell Proliferation;
Gene Expression Regulation, Neoplastic
- From:
Journal of Southern Medical University
2022;42(10):1476-1485
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To examine the role of miR-16-5p in regulating biological behaviors of paclitaxel- resistant breast cancer cells and its molecular mechanism.
METHODS:The expression of miR-16-5p was examined in 13 pairs of breast cancer and adjacent tissues and in parental SKBR-3 cells and paclitaxel-resistant SKBR-3/PR cells using qRT-PCR. The target genes of miR-16- 5p were predicted by bioinformatic analysis, and their targeted binding was tested using luciferase assay. The cells were transfected with a miR-16-5p mimics, a miR-16-5p inhibitor, a specific siRNA targeting YWHAQ (si-YWHAQ), or both the miR-16-5p mimics and si-YWHAQ, and the changes in cellular expressions of YWHAQ, Bcl-2 and Bax were detected using Western blot. The changes in proliferation and migration of the cells were evaluated with CCK-8 assay and Transwell assay, and the cell cycle changes and cell apoptosis were analyzed with flow cytometry.
RESULTS:The expression of miR-16-5p was significantly lower in breast cancer tissues than in paired adjacent tissues (P < 0.01). Bioinformatic analysis predicted that YWHAQ was the target gene of miR-16-5p, which was confirmed by luciferase assay. Compared with parental SKBR- 3 cells, SKBR- 3/PR cells showed a lowered level of miR-16-5p expression and an increased expression of YWHAQ. Transfection with the miR-16-5p mimics significantly inhibited YWHAQ expression (P < 0.01), while miR-16-5p inhibitor promoted YWHAQ expression in SKBR-3/PR cells (P < 0.01). The miR-16-5p mimics caused cell cycle arrest in G0/G1 phase (P < 0.0l), suppressed proliferation and migration, and increased apoptosis rate of SKBR-3/PR cells (P < 0.0l). Knocking down YWHAQ also reduced the migration ability of SKBR-3/PR cells and increased cell apoptosis rate. Transfection with either miR-16-5p mimics or si-YWHAQ resulted in increased Bax expression and lowered expressions of YWHAQ and Bcl-2 in the cells. The cells transfected with both miR-16-5p mimics and si-YWHAQ showed obviously suppressed cell migration (P < 0.01) and significantly increased apoptosis rate (P < 0.01).
CONCLUSION:miR-16-5p can modulate the expressions of Bcl- 2 and Bax by targeted regulation of YWHAQ to modify the biological behaviors of paclitaxel-resistant breast cancer cells.
