Experimental study and clinical significance of AR/let-7 signaling pathway in inhibiting the proliferation of triple negative breast cancer
10.3760/cma.j.issn.1674-6090.2019.05.006
- VernacularTitle:AR/let-7信号通路抑制三阴性乳腺癌增殖的实验研究和临床意义
- Author:
Xiang LU
1
;
Caiping CHEN
Author Information
1. 嘉兴市第一医院乳腺病科 314001
- Keywords:
Triple negative breast cancer;
Androgen receptor;
microRNA;
let-7;
MDA-MB-453 cancer cell;
TCGA database
- From:
Chinese Journal of Endocrine Surgery
2019;13(5):378-382
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the mechanism of AR/let-7 signaling pathway in inhibiting the proliferation of TNBC and its significance for survival.Methods Human breast cancer MDA-MB-453 cells were cultured in vitro and divided into experimental group and control group.The experimental group was added with androgen dihydrotestosterone(DHT),and the control group was added nothing.The cell proliferation was detected by CCK-8,cell cycle was detected by flow cytometry,AR expression was detected by Western blot,and let-7 expression was detected by real-time fluorescent quantitative PCR.The AR,let-7 expression data and survival data of TNBC patients were downloaded from the Cancer Genomes Atlas (TCGA).The expression of AR and let-7 between cancer tissues and normal breast tissues and their relationship with survival was analyzed.Results Cellular experiments showed that the proliferation rate of cancer cells in the experimental group was significantly lower than that in the control group(1.22±0.11 vs 2.26±0.23,t=7.065,P＜0.05),and the ratio of G1/S in the experimental group was greater than in the control group (1.08±0.03 vs 0.68±0.03,t=17.321,P=0.000).The AR and let-7a,b,c,and d were overexpressed in the experimental group.The TCGA data showed that AR,let-7a-1,let-7a-2,let7a-3,and let-7c were lower in breast cancer tissues than in normal tissues (P＜0.05),while let-7d was higher in breast cancer tissues (P＜0.05).The AR,let-7a-1,let-7a-2,let-7a-3,and let-7c were used to cluster the patients into high-expression group and low-expression group,and the overall survival in the high-expression group appeared to be higher,while the difference was not statistically significant (P=0.163).Conclusions The AR/let-7 signaling pathway is up-regulated by DHT activation,which blocks cells in the G1 phase and inhibits cell proliferation.Patients with high expression of AR,let-7a-1,let-7a-2,let-7a-3,and let-7c may have better overall survival.It is suggests that the AR/let-7 signaling pathway may become a new target for TNBC.
