Effect of miR-145 targeting ADAM17 on the growth of triple-negative breast cancer xenografts in nude mice and associated mechanism
10.13406/j.cnki.cyxb.003836
- VernacularTitle:miR-145靶向ADAM17对裸鼠三阴性乳腺癌移植瘤生长的影响及机制
- Author:
Yaning MIAO
1
;
Guannan YANG
;
Xuepeng ZHANG
;
Hongzhou SHANG
;
Baoshan HU
;
Li YAN
Author Information
1. 华北理工大学附属医院肿瘤外科,唐山 063000
- Keywords:
micro RNA-145;
a disintegrin and metalloprotease 17;
triple-negative breast cancer;
targeted therapy
- From:
Journal of Chongqing Medical University
2025;50(8):1047-1052
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the effect of applying the analog of miR-145(agomiR-145)to target a disintegrin and metallopro-tease 17(ADAM17)on the growth of triple-negative breast cancer(TNBC)xenograft tumors in nude mice and the underlying mecha-nism.Methods:A subcutaneous xenograft tumor model was established in nude mice with MDA-MB-231 cells(n=30).The 30 nude mice were randomly divided into agomiR group,agomiR-NC group,and control group to receive intratumoral injection of 100 μL of agomiR-145(0.33 g/L),agomiR-NC(0.33 g/L),and normal saline,respectively.We examined tumor tissue morphology with HE stain-ing;measured the expression of miR-145,ADAM17,and epidermal growth factor receptor(EGFR)in tumor tissues by real-time poly-merase chain reaction(RT-PCR);and determined the protein expression of ADAM17,EGFR,and p-EGFR in tumor tissues by immu-nohistochemistry and Western blot.Results:The tumor growth in the agomiR group was slow,with a significantly smaller tumor volume than those in the control group and the agomiR-NC group(P<0.05).The results of HE staining showed more severe necrosis and hem-orrhage within tumor tissues in the control group and the agomiR-NC group than in the agomiR group.RT-PCR results showed that the expression level of miR-145 in the agomiR group was significantly higher than those in the agomiR-NC and control groups(P<0.001);the agomiR group had a significantly lower mRNA expression level of ADAM17 than the other two groups(P<0.05);and there was no significant difference in EGFR mRNA expression between the three groups(P>0.05).Immunohistochemistry and Western blot detected significantly lower protein expression levels of ADAM17 and EGFR in the agomiR group than in the agomiR-NC group and the control group(P<0.05).Conclusion:AgomiR-145 inhibits the growth of TNBC xenografts in nude mice by targeted suppression of ADAM17-EGFR activity.
