Journal
ONCOTARGETS AND THERAPY
Volume 13, Issue -, Pages 6873-6884Publisher
DOVE MEDICAL PRESS LTD
DOI: 10.2147/OTT.S256153
Keywords
miR-27a-3p; chemoresistance; breast cancer; adriamycin; BTG2
Categories
Funding
- Social Development Foundation of Science and Technology of Jiangsu [BE2016658]
- Changzhou Sci Tech Program [CE20165020]
- High-Level Medical Talents Training Project of Changzhou [2016CZLJ007]
- Project of Changzhou medical innovation team [CCX201807]
- Natural Science Foundation of China [81702591]
- Natural Science Foundation of Jiangsu Province [BK20170294]
Ask authors/readers for more resources
Aim: This study aimed to explore the regulative mechanisms of miR-27a-3p in chemoresistance of breast cancer cells. Materials and Methods: qRT-PCR was employed to determine miR-27a-3p expression in two breast cancer cell lines, MCF-7 and MCF-7/adriamycin-resistant cell line (MCF-7/ADR). The two cell lines were treated with miR-27a-3p mimics or inhibitors or corresponding negative control (NC), respectively. The changes were investigated by qRT-PCR, CCK-8 assay, Western blot (WB), colony formation assay, and flow cytometry assay. Moreover, luciferase reporter assay was analyzed to verify the downstream target gene of miR-27a-3p. Further investigation in the correlation between miR-27a-3p and BTG2 was launched by WB, flow cytometry assay, and CCK-8 assay. The expression of Akt and p-Akt was detected by WB. Key Findings: Significantly higher miR-27a-3p expression was confirmed in MCF-7/ADR as compared with sensitive cell line MCF-7 (P<0.05). The down-regulation of miR-27a-3p in MCF-7/ADR enhanced the sensitivity of cancer cells to adriamycin treatment, decreased multidrug resistance gene 1/P-glycoprotein (MDR1/P-gp) expression, enhanced the apoptosis-related proteins expression, increased adriamycin-induced apoptosis, and inhibited cell proliferation as compared to NC groups (P<0.05). The up-regulation of miR-27a-3p in MCF-7 showed the opposite results. BTG2 is identified as a direct target of miR-27a-3p and its down-regulation reversed ADR-resistance. BTG2 treatment exhibited inhibitory effect on PI3K/Akt pathway in MCF-7/ADR cells. Significance: miR-27a-3p might be associated with resistance of breast cancer cells to adriamycin treatments, modulating cell proliferation and apoptosis by targeting BTG2 and promoting the PI3K/Akt pathway in breast cancer cells. miR-27a-3p/BTG2 axis might be a potential therapeutic target for clinical BC resistance.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available