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DNAJB4 suppresses breast cancer progression and promotes tumor immunity by regulating the Hippo signaling pathway

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资源类型：
Pubmed体系：
作者：
Chen Yanru[1,2] * ; Li Jingjia[1,2] * ; Pu Lulan[1,2] * ; Hu Jinghua[1,2] ; Fang Lingyu[1,2] ; Zhou Fangfang[1,2] ; Zhang Hongying[3] ; Yang Yi[1,2] ; Rong Xinxin[1,2] ; Deng Shishan[1,2] ; Hou Lingmi[1,2] ;
机构： [1]Academician (Expert) Workstation, Medical Imaging Key Laboratory of Sichuan Province, Biological Targeting Laboratory of Breast Cancer, Department of Breast and Thyroid Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China. [2]Medical Imaging Key Laboratory of Sichuan Province, Institute of Basic Medicine and Forensic Medicine, North Sichuan Medical College, Nanchong, Sichuan, China. [3]The Fifth People’s Hospital of Nanchong City, Nanchong, Sichuan, China
出处：
DOI： 10.1007/s12672-023-00762-8

关键词： Breast cancer DNAJB4 Migration Proliferation Hippo pathway Tumor immunity

摘要：
Breast cancer is the most common cancer worldwide. Low DNAJB4 expression levels are strongly correlated with poor prognosis in breast cancer patients. However, the molecular mechanism by which DNAJB4 regulates breast cancer progression is unclear.The expression of DNAJB4 was validated in human breast cancer tissues, normal human breast tissues, and breast cancer cell lines. CCK-8, colony-forming, and wound healing assays were used to assess the biological effect of DNAJB4 overexpression on cell proliferation and migration in MCF-7 cell lines. Bioinformatic analysis was used to identify the DNAJB4 related pathways in breast cancer. Epithelial-mesenchymal transition (EMT)-related biomarkers and Hippo pathway components were quantified by Western blots. Luciferase and Western blot assays were used to validate which miRNA regulates DNAJB4. In addition, the effects of DNAJB4 on in vivo tumor growth were assessed in xenograft models.DNAJB4 was expressed at low levels in human breast cancer tissues and breast cancer cell lines and correlated with poor prognosis. DNAJB4 overexpression significantly inhibited cell proliferation and migration in vitro by activating the Hippo pathway. The dual-luciferase assay showed that hsa-miR-183-5p targeted DNAJB4. Moreover, the effects of DNAJB4 could be reversed by miR-183-5p. In addition, the expression of DNAJB4 was strongly correlated with immune infiltration levels. Notably, DNAJB4 overexpression markedly enhanced CD4 + and CD8 + T cells and reduced PD-L1 levels in 4T1 tumors via the Hippo pathway, which retarded tumor growth in a subcutaneous xenograft tumor mouse model of 4T1 cells.The present study demonstrated that DNAJB4 overexpression inhibited the malignant biological behavior of breast cancer by regulating the Hippo pathway and tumor immunosuppressive environment.© 2023. Springer Science+Business Media, LLC.

基金：
This work was supported by the Natural Science Foundation of Sichuan province (No. 2022NSFSC0775), Research development plan of Affiliated Hospital of North Sichuan Medical College (No. 2022JC021), Sichuan Province Science and Technology Innovation seedling project (No. 2022069), North Sichuan Medical College ’s scientific research project (No. CBY22-QNA01, No. CBY20-QA-Z13), Opening Project of Medical Imaging Key Laboratory of Sichuan Province (No. MIKL202206).
语种：
外文
PubmedID：
第一作者：
第一作者机构： [1]Academician (Expert) Workstation, Medical Imaging Key Laboratory of Sichuan Province, Biological Targeting Laboratory of Breast Cancer, Department of Breast and Thyroid Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China. [2]Medical Imaging Key Laboratory of Sichuan Province, Institute of Basic Medicine and Forensic Medicine, North Sichuan Medical College, Nanchong, Sichuan, China.
共同第一作者：
通讯作者：
通讯机构： [1]Academician (Expert) Workstation, Medical Imaging Key Laboratory of Sichuan Province, Biological Targeting Laboratory of Breast Cancer, Department of Breast and Thyroid Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China. [2]Medical Imaging Key Laboratory of Sichuan Province, Institute of Basic Medicine and Forensic Medicine, North Sichuan Medical College, Nanchong, Sichuan, China.
推荐引用方式(GB/T 7714)：
Chen Yanru,Li Jingjia,Pu Lulan,et al.DNAJB4 suppresses breast cancer progression and promotes tumor immunity by regulating the Hippo signaling pathway[J].Discover. Oncology.2023,14(1):144.doi:10.1007/s12672-023-00762-8.
APA：
Chen Yanru,Li Jingjia,Pu Lulan,Hu Jinghua,Fang Lingyu...&Hou Lingmi.(2023).DNAJB4 suppresses breast cancer progression and promotes tumor immunity by regulating the Hippo signaling pathway.Discover. Oncology,14,(1)
MLA：
Chen Yanru,et al."DNAJB4 suppresses breast cancer progression and promotes tumor immunity by regulating the Hippo signaling pathway".Discover. Oncology 14..1(2023):144

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