三阴性乳腺癌(TNBC)是当前没有有效定向治疗的最恶性亚型乳腺癌。DNAJB4(Dnaj热休克蛋白家族(Hsp40)成员B4)是人的热休克蛋白家族(Hsp40)的成员。我们以前的研究报告了DNAJB4在乳腺癌中的临床意义。然而，DNAJB4在TNBC细胞凋亡中的生物学功能至今仍不清楚。通过定量实时聚合酶链反应(qRT-PCR)和西方印迹分析，量化了正常乳腺细胞、乳腺癌细胞、四对TNBC组织和相邻非癌组织中DNAJB4的表达。使用一系列体内外的增益和失去功能实验，研究了DNAJB4在TNBC细胞凋亡中的作用。通过西方印迹分析阐明了TNBC细胞凋亡的基本分子机制。DNAJB4在TNBC组织和细胞系中表达显著下降。DNAJB4的沉默抑制了TNBC细胞凋亡并促进了体外和体内的肿瘤生成，而DNAJB4的过表达则产生了相反的作用。在机械上，DNAJB4的沉默通过抑制Hippo信号转导通路抑制了TNBC细胞凋亡，而DNAJB4的过表达则导致了相反的结果。DNAJB4通过激活Hippo信号转导通路促进TNBC细胞凋亡。因此，DNAJB4可能作为TNBC的预后生物标志物和治疗靶点。（2023年。作者（们）。）

Triple-negative breast cancer (TNBC) is currently the most malignant subtype of breast cancer without effective targeted therapies. DNAJB4 (Dnaj heat shock protein family (Hsp40) member B4) is a member of the human heat shock protein family (Hsp40). The clinical significance of DNAJB4 in breast cancer has been reported in our previous study. However, the biological function of DNAJB4 in TNBC cell apoptosis remains unclear to date.The expression of DNAJB4 in normal breast cells, breast cancer cells, four-paired TNBC tissues, and adjacent noncancerous tissues was quantified by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot assay. The role of DNAJB4 in TNBC cell apoptosis was investigated using a number of gain- and loss-of-function in vitro and in vivo assays. The underlying molecular mechanisms in TNBC cell apoptosis were elucidated via Western blot assay.DNAJB4 expression was significantly downregulated in TNBC tissues and cell lines. DNAJB4 knockdown inhibited TNBC cell apoptosis and promoted tumorigenicity in vitro and in vivo, but DNAJB4 overexpression resulted in the opposite. Mechanically, DNAJB4 knockdown inhibited TNBC cell apoptosis through suppression of the Hippo signaling pathway, and the result was reversed after DNAJB4 overexpression.DNAJB4 promotes TNBC cell apoptosis by activating the Hippo signaling pathway. Therefore, DNAJB4 may act as a prognostic biomarker and therapeutic target for TNBC.© 2023. The Author(s).