Background: Breast cancer (BC) is the leading cause of tumor-related death in women worldwide, but its pathogenesis is not clear. The efficient screening of new therapeutic targets for BC through bioinformatics and biological experimental techniques has become a hot topic in BC research. Methods:The bioinformatics method was used to analyze the gene chips and obtain the hub genes, playing an important role in the development of BC. The biological processes (BP) involved in the hub genes were analyzed by Bingo, and the impact of each hub gene on disease-free survival (DFS) and overall survival (OS) in BC patients was evaluated in the Kaplan-Meier Plotter database. The expression of DNAJB4, the hub gene with the greatest degree and having an effect on the prognosis of BC patients, was detected in BC cell lines and clinicopathological specimens. And DNAJB4 was selected for further biological experiments and clinical prognosis verification.Results: Ten hub genes including DNAJB4, the greatest degree genes, were found by bioinformatics analysis of BC gene chips. DNAJB4 expressions in both BC cell lines and clinicopathological specimens were detected and the results showed that DNAJB4 was significantly down-regulated in BC cell lines and tissues.After interfering with the expression of DNAJB4, it was found that the invasion and migration ability of MDA-MB-231 cell line was significantly enhanced in vitro. The clinical survival data of BC patients showed that patients with high DNAJB4 expression had longer DFS.Conclusions: DNAJB4 may be a tumor suppressor gene in BC as it could regulate invasion and migration of BC cells and its expression level is related to the prognosis of BC patients. Nevertheless, further researches are still necessary to verify its role in BC so as to provide evidences for clinical guidance regarding diagnosis and treatment.

Introduction 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. Methods 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. Results 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. Conclusions DNAJB4 promotes TNBC cell apoptosis by activating the Hippo signaling pathway. Therefore, DNAJB4 may act as a prognostic biomarker and therapeutic target for TNBC.