乳腺癌是全球最常见的癌症。DNAJB4表达水平降低与乳腺癌患者预后不良密切相关。然而，DNAJB4调节乳腺癌进展的分子机制尚不清楚。本研究验证了DNAJB4在人类乳腺癌组织、正常人类乳腺组织和乳腺癌细胞系中的表达情况。利用CCK-8、形成菌落和伤口愈合实验评估了DNAJB4过表达对MCF-7细胞系增殖和迁移的生物学影响。采用生物信息学分析鉴定了DNAJB4在乳腺癌中的相关通路。通过Western印迹法定量检测上皮-间质转化（EMT）相关生物标志物和Hippo通路组分。利用荧光素酶和Western印迹实验证明哪种miRNA调节DNAJB4。此外，使用异种移植模型评估了DNAJB4对体内肿瘤生长的影响。结果显示，DNAJB4在人类乳腺癌组织和乳腺癌细胞系中表达水平较低并与预后不良相关。DNAJB4过表达通过激活Hippo通路显著抑制了体外细胞增殖和迁移。双荧光素酶实验显示hsa-miR-183-5p靶向DNAJB4。此外，miR-183-5p能够逆转DNAJB4的效果。另外，DNAJB4表达与免疫浸润水平强烈相关。值得注意的是，DNAJB4过表达通过Hippo通路显著增强了4T1瘤中CD4+和CD8+ T细胞的水平，并降低PD-L1水平，减缓了4T1细胞皮下异种移植瘤小鼠模型中的肿瘤生长。本研究证明了DNAJB4过表达通过调控Hippo通路和肿瘤免疫抑制环境抑制了乳腺癌的恶性生物学行为。© 2023. Springer Science+Business Media, LLC.

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.