Zinc Finger SWIM-Type Containing 3 Reprograms Lipid Metabolism and Drives Breast Cancer Progression.

Background: Zinc finger proteins (ZNFs) have been proved to play important roles in driving the progression of breast cancer (BC), one of the most common cancers among women. This study aimed to investigate the involvement of zinc-finger SWIM domain-containing protein 3 () in promoting BC cell progression by regulating lipid metabolism.

Methods: Differential expression of in BC was confirmed by comparing its expression in normal human mammary epithelial cells and BC cells. MCF7 cells, a BC cell line, were subjected to knockdown/overexpression experiments. The lipid contents in MCF7 cells were measured by assay kits and immunofluorescence test. The lipogenic enzymes in the cells were detected by enzyme-linked immunosorbent assay (ELISA). The cells were also subjected to further transfection experiments to manipulate the expression of sterol regulatory element-binding transcription factor 1 ()/ in -regulated MCF7 cells to verify whether the targets . Subsequently, the lipid contents in the transfected cells were determined, and the cell viability, proliferation and metastasis were measured.

Results: was overexpressed in BC cells. knockdown/overexpression led to a significant decrease/increase of the lipid contents including triglyceride, free fatty acid, cholesterol, phospholipid and neutral lipid, and lipogenic enzymes ( < 0.01). The knockdown decreased the expression of and ( < 0.01). Our findings showed that lipid content reduction induced by knockdown was reversed by overexpression. MCF7 cell viability, proliferation and metastasis, which were all suppressed by knockdown ( < 0.001), were reversible through overexpression ( < 0.001). On the other hand, the overexpression increased and expression ( < 0.001). Lipid content elevation, as well as increased MCF7 cell viability, proliferation and metastasis, which were induced by overexpression, could be counteracted by downregulation ( < 0.001).

Conclusion: promotes BC progression by enhancing lipid synthesis. This study reveals the malevolent effect of on BC, underpinned by the reprogramming of lipid metabolism, providing insights into potential therapeutic targets for BC treatments.