RelB is a subunit of NF-кB signaling famliy and appears aberrant expression in breast cancer. The aim of the present study was to further investigate the role of RelB in breast cancer and whether RelB might be a therapeutic target.
120 breast cancer patients were collected from Jiangsu Province Hospital during 2015-2017. IHC was performed to detect RelB expression in breast cancer tissues and para-cancer tissues. The relationship between RelB expression and clinical pathologic parameters were investigated. Detection the expression of RelB in MCF-7, T47D, MDA-MB-231, BT-549 breast cancer cell lines by Western blot and RT-qPCR. Knockout of RelB in BT-549 and MDA-MB-231 cells was using the CRISPR/Cas9 genome editing system. CCK-8 and flow cytometry were performed to observe the proliferation, cycle and apoptosis of cells. Transwell and wound healing were used to observe cell invasion and migration. RT-PCR and Western blotting were performed to detect the expression of mRNA and protein of EMT and MMP1. The luciferase reporter gene was performed to detect whether RelB binding with MMP1. In vivo efficacy was tested using the xenograft model and lung metastasis model.
RelB was highly expressed in TNBC tissues compared with that in adjacent tissues. RelB levels were remarkably associated with the pTNM stage (p = 0.02) and ER expression (p = 0.46). RelB expressions in TNBC cells were higher than that in MCF-7 cells. In vitro studies showed that RelB deletion promoted apoptosis and suppressed breast cancer cell survival, migration and invasion by decreasing snail, vimentin and MMP1. RelB deletion inhibited cell cycle progression and G1/S transition by upregulating p21 and p27 expression. In vivo studies showed that 231-RelB-KO cells completely impaired tumor formation in xenograft models and lung metastasis model in nude mice.
RelB is aberrant constitutive expressed in clinical specimens and cell lines of breast cancer, especially in TNBC. RelB regulates malignant phenotypes of breast cancer, including cell survival, apoptosis, cell cycle, migration and invasion. Moreover, RelB can induce MMP1, which facilitates the invasion of tumor. Collectively, our findings highlight that RelB might serve as a therapeutic target for TNBC.
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All authors have declared no conflicts of interest.