Effect of miR-145 targeting ADAM17 on the growth of triple-negative breast cancer xenografts in nude mice and associated mechanism

Miao Yaning; Yang Guannan; Zhang Xuepeng; Shang Hongzhou; Hu Baoshan; Yan Li

doi:10.13406/j.cnki.cyxb.003836

您当前的位置：

首页 >

文章列表页 >

Effect of miR-145 targeting ADAM17 on the growth of triple-negative breast cancer xenografts in nude mice and associated mechanism

Precision medicine in cancer and translational studies | 更新时间：2025-10-22

- Effect of miR-145 targeting ADAM17 on the growth of triple-negative breast cancer xenografts in nude mice and associated mechanism
- Journal of Chongqing Medical University Vol. 50, Issue 8, Pages: 1047-1052(2025)
- 作者机构：
  
  1.华北理工大学附属医院肿瘤外科，唐山 063000
  2.华北理工大学材料科学与工程学院，唐山 063210
- 作者简介：
- 基金信息：
- DOI：10.13406/j.cnki.cyxb.003836
  CLC： R737.9
- Received：16 January 2025，
  
  Revised：2025-03-09，
  
  Accepted：20 March 2025，
  
  Published：28 August 2025
- 稿件说明：
移动端阅览
苗雅宁,杨冠楠,张雪鹏,等.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[J].重庆医科大学学报,2025,50(8):1047-1052.

Miao Yaning,Yang Guannan,Zhang Xuepeng,et al.Effect of miR-145 targeting ADAM17 on the growth of triple-negative breast cancer xenografts in nude mice and associated mechanism[J].Journal of Chongqing Medical University,2025,50(8):1047-1052.
苗雅宁,杨冠楠,张雪鹏,等.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[J].重庆医科大学学报,2025,50(8):1047-1052. DOI： 10.13406/j.cnki.cyxb.003836.

Miao Yaning,Yang Guannan,Zhang Xuepeng,et al.Effect of miR-145 targeting ADAM17 on the growth of triple-negative breast cancer xenografts in nude mice and associated mechanism[J].Journal of Chongqing Medical University,2025,50(8):1047-1052. DOI： 10.13406/j.cnki.cyxb.003836.

摘要

目的

探讨miR-145的模拟类似物agomiR-145靶向解聚素-金属蛋白酶17（a disintegrin and metalloprotease 17，ADAM17）对裸鼠三阴性乳腺癌（triple negative breast cancer，TNBC）移植瘤生长的影响及其作用机制。

方法

构建MDA-MB-231细胞裸鼠皮下移植瘤模型（

=30），将30只裸鼠随机分为agomiR组、agomiR-NC组和对照组，分别瘤内注射0.33 g/L的agomiR-NC、agomiR-145 100 µL和等量生理盐水。苏木精-伊红染色法（hematoxylin-eosin staining，HE）染色观察组织形态，实时荧光定量PCR（real-time polymerase chain reaction，RT-PCR）检测各瘤体组织miR-145、ADAM17及表皮生长因子受体（epidermal growth factor receptor，EGFR）的表达，免疫组化与蛋白免疫印迹法（Western blot）分析ADAM17、EGFR及p-EGFR蛋白表达。

结果

agomiR组瘤体生长缓慢，明显小于对照组和agomiR-NC组（

0.05）。HE结果显示对照组和agomiR-NC组肿瘤组织相较于agomiR组坏死和出血更为严重。RT-PCR结果表明agomiR组miR-145表达较agomiR-NC组和对照组明显上升（

0.001）；agomiR组ADAM17 mRNA表达明显小于agomiR-NC组和对照组（

0.05）；3组EGFR mRNA表达差异无统计学意义（

0.05）。免疫组化和Western Blot结果均显示agomiR组ADAM17和EGFR的蛋白表达明显低于agomiR-NC组及对照组（

0.05）。

结论

miR-145通过靶向抑制ADAM17-EGFR的活性抑制裸鼠TNBC移植瘤的生长。

Abstract

Objective

To investigate the effect of applying the analog of miR-145（agomiR-145） to target a disintegrin and metalloprotease 17（ADAM17） on the growth of triple-negative breast cancer（TNBC） xenograft tumors in nude mice and the underlying mechanism.

Methods

A subcutaneous xenograft tumor model was established in nude mice with MDA-MB-231 cells（

=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 staining； measured the expression of miR-145，ADAM17，and epidermal growth factor receptor（EGFR） in tumor tissues by real-time polymerase chain reaction（RT-PCR）； and determined the protein expression of ADAM17，EGFR，and p-EGFR in tumor tissues by immunohistochemistry 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（

0.05）. The results of HE staining showed more severe necrosis and hemorrhage 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（

0.001）；the agomiR group had a significantly lower mRNA expression level of ADAM17 than the other two groups（

0.05）；and there was no significant difference in EGFR mRNA expression between the three groups（

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（

0.05）.

Conclusion

AgomiR-145 inhibits the growth of TNBC xenografts in nude mice by targeted suppression of ADAM17-EGFR activity.

关键词

Keywords

references

Saad MI ， Jenkins BJ . The protease ADAM17 at the crossroads of disease：revisiting its significance in inflammation，cancer，and beyond [J ] . FEBS J ， 2024 ， 291 （ 1 ）： 10 - 24 ．

Wang K ， Xuan ZX ， Liu XY ， et al . Immunomodulatory role of metalloproteinase ADAM17 in tumor development [J ] . Front Immunol ， 2022 ， 13 ： 1059376 ．

Yang G ， Cui MY ， Jiang WB ， et al . Molecular switch in human diseases-disintegrin and metalloproteinases，ADAM17 [J ] . Aging（Albany NY）， 2021 ， 13 （ 12 ）： 16859 - 16872 ．

张　兰，郑　健，张雪鹏，等 . miR-145通过调控解聚素-金属蛋白酶17对MCF-7乳腺癌细胞的影响 [J ] . 医学研究生学报， 2019 ， 32 （ 11 ）： 1169 - 1173 ．

Zhang L ， Zheng J ， Zhang XP ， et al . Effect of miR-145 on MCF-7 breast cancer cells by regulating disintegrin-metalloproteinase-17 [J ] . J Med Postgrad ， 2019 ， 32 （ 11 ）： 1169 - 1173 ．

朱凌霄，张　兰，张雪鹏，等 . miR-145对三阴性乳腺癌细胞增殖、侵袭及转移能力的影响 [J ] . 中国医药导报， 2021 ， 18 （ 32 ）： 22 - 27 ．

Zhu LX ， Zhang L ， Zhang XP ， et al . Effect of miR-145 on the proliferation，invasion and migration of triple-negative breast cancer cells [J ] . China Med Her ， 2021 ， 18 （ 32 ）： 22 - 27 ．

李　岩，王兴河 . 基于生物信息学分析三阴性乳腺癌的差异表达基因和药物靶点挖掘 [J ] . 中国临床药理学杂志， 2024 ， 40 （ 2 ）： 269 - 272 ．

Li Y ， Wang XH . Effects of Astragalus polysaccharide on proliferation and invasion of triple negative breast cancer cells [J ] . Chin J Clin Pharmacol ， 2024 ， 40 （ 2 ）： 269 - 272 ．

Jiang YZ ， Ma D ， Suo C ， et al . Genomic and transcriptomic landscape of triple-negative breast cancers：subtypes and treatment strategies [J ] . Cancer Cell ， 2019 ， 35 （ 3 ）： 428 - 440 .

Zagami P ， Carey LA . Triple negative breast cancer：Pitfalls and progress [J ] . NPJ Breast Cancer ， 2022 ， 8 （ 1 ）： 95 ．

Mustafa M ， Abbas K ， Alam M ， et al . Molecular pathways and therapeutic targets linked to triple-negative breast cancer （TNBC） [J ] . Mol Cell Biochem ， 2024 ， 479 （ 4 ）： 895 - 913 ．

Leon-Ferre RA ， Goetz MP . Advances in systemic therapies for triple negative breast cancer [J ] . BMJ ， 2023 ， 381 ： e071674 ．

Vagia E ， Mahalingam D ， Cristofanilli M . The landscape of targeted therapies in TNBC [J ] . Cancers （Basel）， 2020 ， 12 （ 4 ）： 916 ．

Gupta S ， Silveira DA ， Piedade GPS ， et al . A dynamic Boolean network reveals that the BMI1 and MALAT1 axis is associated with drug resistance by limiting miR-145-5p in non-small cell lung cancer [J ] . Noncoding RNA Res ， 2023 ， 9 （ 1 ）： 185 - 193 ．

Hu CC ， Liu TY ， Zhang WX ， et al . miR-145 inhibits aerobic glycolysis and cell proliferation of cervical cancer by acting on MYC [J ] . FASEB J ， 2023 ， 37 （ 4 ）： e22839 ．

Luo BF ， Yuan Y ， Zhu YF ， et al . microRNA-145-5p inhibits prostate cancer bone metastatic by modulating the epithelial-mesenchymal transition [J ] . Front Oncol ， 2022 ， 12 ： 988794 ．

Venkatesh J ， Wasson MD ， Brown JM ， et al . LncRNA-miRNA axes in breast cancer：Novel points of interaction for strategic attack [J ] . Cancer Lett ， 2021 ， 509 ： 81 - 88 ．

Contreras-Sanzón E ， Carlos-Reyes Á ， Sierra-Martínez M ， et al . Metastatic breast tumors downregulate miR-145 regulating the hypoxia-induced vasculogenic mimicry [J ] . Transl Oncol ， 2023 ， 33 ： 101680 ．

Wang XA ， Ma J ， Lin DM ， et al . MiR-145-5p reduced ANG Ⅱ-induced ACE2 shedding and the inflammatory response in alveolar epithelial cells by targeting ADAM17 and inhibiting the AT1R/ADAM17 pathway [J ] . Eur J Pharmacol ， 2024 ， 971 ： 176392 ．

Yang JT ， Lee IN ， Huang C ， et al . ADAM17 confers temozolomide resistance in human glioblastoma cells and miR-145 regulates its expression [J ] . Int J Mol Sci ， 2023 ， 24 （ 9 ）： 7703 ．

Wu J ， Yin L ， Jiang N ， et al . MiR-145，a microRNA targeting ADAM17，inhibits the invasion and migration of nasopharyngeal carcinoma cells [J ] . Exp Cell Res ， 2015 ， 338 （ 2 ）： 232 - 238 ．

孟祥潮，蔡　准，陈国福，等 . ADAM17-shRNA对人乳腺癌MCF-7细胞增殖的影响及机制 [J ] . 山东医药， 2017 ， 57 （ 4 ）： 21 - 24 ．

Meng XC ， Cai Z ， Chen GF ， et al . Effects of ADAM17-shRNA on proliferation of human breast cancer MCF-7 cells [J ] . Shandong Med J ， 2017 ， 57 （ 4 ）： 21 - 24 ．

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Advances in antibody-drug conjugate in the treatment of urothelial carcinoma

Advances in and reflections on bacteria-mediated oncology therapy

Research advances in cancer-associated fibroblasts in targeted tumor therapy

Invasion and metastasis of triple-negative breast cancer mediated by the PSME3-NF-kappaB pathway

Related Author

Bai Xuesong

Yin Hubin

Kuang Youlin

Gou Xin

Zhu Ying

Wang Zining

Gu Wei

Luo Yang

Related Institution

Department of Urology，The First Affiliated Hospital of Chongqing Medical University

Center for Intelligent Testing and Molecular Medicine， School of Medicine， Chongqing University

Department of Gastrointestinal Surgery，The First Affiliated Hospital of Guangxi Medical University

Key Laboratory for Oral Biomedical Engineering in Chongqing

Institute of Ultrasound Imaging,Chongqing Medical University

⁰