High expression of ZNF652 promotes carcinogenesis and progression of breast cancer

Abstract

To investigate the expression of ZNF652 in breast cancer tissues and cells and explore its role in breast cancer cell proliferation, invasion and migration. We exploited the data from the TCGA database to analyze the differential expression of ZNF652 in breast cancer tissues and adjacent tissues and the correlations of ZNF652 expression with the clinicopathological characteristics of breast cancer patients including molecular subtypes, pathological types, TNM stages and clinical stages. RT-qPCR and Western blotting were used to detect the expression of ZNF652 in 5 breast cancer cell lines including MCF-7, MDA-MB-231, SK-BR-3, UACC-812 and BT-474. Using a lentivirus system and siRNA technique, we assessed the effects of ZNF652 over-expression and knockdown on proliferation, colony forming ability, migration and invasion of breast cancer cells with CCK-8 assay, clonogenic assay, Transwell assay and wound healing assay. The subcellular localization of ZNF652 in 293T cells was determined using immunofluorescence assay. ZNF652 was significantly up-regulated in breast cancer tissues (P < 0.001). In breast cancer tissues of different molecular types, ZNF652 was down-regulated in TNBC breast cancer tissues but increased in HER2+, Luminal A and Luminal B breast cancer tissues (P < 0.01 or 0.001). The expression of ZNF652 was significantly higher in breast cancer tissues of all pathological types except for mucinous carcinoma than in the adjacent tissues (P < 0.05). The high expression of ZNF652 was closely related to distant metastasis and malignancy of breast cancer (P < 0.01 or 0.001). The mRNA and protein expression levels of ZNF652 was significantly higher in the 5 breast cancer cell lines than in normal breast cells (P < 0.05 or 0.001). Overexpression of ZNF652 promoted the proliferation, invasion and migration of breast cancer cells, while ZNF652 knockdown produced the opposite effects (P < 0.05). Immunofluorescence assay identified subcellular localization of ZNF652 in the nuclei of 293T cells. ZNF652 is highly expressed in breast cancer tissues and cells to promote the development and progression of breast cancer and may serve as a potential molecular target for diagnosis and treatment of the malignancy.