DNASE1L2, as a Carcinogenic Marker, Affects the Phenotype of Breast Cancer Cells Via Regulating...

The authors explore the role of DNASE1L2 in breast cancer (BC) and its affect on the cell phenotype. Breast invasive ductal carcinoma RNA-Seq data set was downloaded from The Cancer Genome Atlas database for analyzing DNASE1L2 levels. Overall survival curve was plotted by Kaplan-Meier methods. The correlations between DNASE1L2 expression and clinical characteristics were analyzed by chi-square tests. Cox regression models were implemented for analyzing the potential prognosticators of BC. Small interference RNA-DNASE1L2 and pcDNA3.1-DNASE1L2 were transfected into BC cells to silence and overexpress DNASE1L2, respectively. Relative mRNA and protein levels were determined by quantitative real-time PCR (qRT-PCR) and Western blot, respectively. Cell counting Kit-8, clone formation, and Transwell assays were employed to measure the proliferative, invasive, and migratory abilities. Bioinformatics analysis showed that the levels of DNASE1L2 were found to be elevated in BC tissues, which was further proved by qRT-PCR tests. Besides, high expression of DNASE1L2 was dramatically led to a poor overall survival. Furthermore, DNASE1L2 expression was remarkably associated with age and pathologic-stage. Silencing DNASE1L2 showed an inhibitory effect on the proliferation, invasion, and migration of MCF7 cells, whereas overexpression of DNASE1L2 in BT549 cells presented the opposite results. Mechanistically, downregulation of DNASE1L2 could significantly enhance the levels of E-cadherin, as well as suppress the levels of Vimentin, N-cadherin and Snail, whereas upregulation of DNASE1L2 showed the reverse outcomes. This study for the first time demonstrated that DNASE1L2 was upregulated in BC cells, and acted as an oncogene to affect the phenotype of BC cells by modulating the epithelial-mesenchymal transition process, which suggested that DNASE1L2 might be considered as a useful biomarker for BC therapeutics.