Nad(P) Dependent Steroid Dehydrogenase-Like, Involved In Cholesterol Biosynthesis, Regulates Proliferation And Metastasis In Breast Cancer

Background: Cholesterol biosynthesis pathway is a common upregulated pathway in breast cancer. NSDHL (NAD(P) Dependent Steroid Dehydrogenase-Like), a gene which is involved in cholesterol biosynthesis has not been elucidated for its role in breast cancer. Methods After knock-down of NSDHL in human breast cancer cell lines, cell proliferation assay, cell cycle analysis, 3D culture, clonogenic assay, migration and invasion assay, and wound healing assay were performed. We tested erlotinib as a target drug for NSDHL. Xenograft was developed with MDA-MB-231 transfected with NSDHL shRNA in NOD/SCID mice. Public gene expression databases were used for the analysis of prognostic role of NSDHL in breast cancer Results Both NSDHL mRNA and protein levels were higher in a Luminal (MCF7) and triple negative cells (MDA-MB-231, BT-20) than normal breast cancer cell (MCF10A). Silencing of NSDHL by siRNA inhibited cell cycle and proliferation, and also inhibited migration and invasion in MDA-MB-231 and BT-20 cells (p< 0.05). The sensitivity to erlotinib was significantly decreased in siNSDHL treated cells, especially in MDA-MB-231 (p<0.01). Additionally, we found that NSDHL regulated total cholesterol levels in breast cancer cells. In vivo xenograft model, NSDHL knock down in the cancer cell decreased the tumor growth and metastasis. Clinically, higher NSDHL expression in the tumor of 3951 breast cancer patients was associated with significantly lower recurrence-free survival. Conclusions In conclusion, we showed that NSDHL might have a role for the progression of breast cancer. Further studies are needed to clarify that NSDHL can be a therapeutic target in breast cancer.