LncRNA DLEU1/microRNA-300/RAB22A axis regulates migration and invasion of breast cancer cells

C. Wang, X.-X. Xie, W.-J. Li, D.-Q. Jiang

Department of Breast Oncology, Cancer Hospital of China Medical University, Shenyang, China. jiangzy968@163.com

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• Oncology

OBJECTIVE: To explore the possible role of deleted in lymphocytic leukemia 1 (DLEU1) in regulating the metastasis of breast cancer and its underlying mechanism.

PATIENTS AND METHODS: The expression levels of DLEU1 in 60 cases of breast cancer tissues and adjacent normal tissues were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Survival analysis and receiver operating characteristic (ROC) curves were introduced to analyze the correlation between DLEU1 expression and the clinical features of enrolled breast cancer patients. After altering expressions of DLEU1, RAB22A or microRNA-300 by plasmid transfection, the abilities of breast cancer cells to migrate and invade were evaluated by transwell assay. Western blot was conducted to detect protein level changes of epithelial-mesenchymal transition (EMT)-related genes regulated by DLEU1, RAB22A or microRNA-300. Dual-luciferase reporter gene assay was performed to detect the binding relation between microRNA-300 with DLEU1 and RAB22A.

RESULTS: DLEU1 expression remains higher in breast cancer tissues than in normal adjacent tissues, and has a certain diagnostic value. The overall survival of breast cancer patients was negatively correlated with DLEU1 expression. Overexpression of DLEU1 or RAB22A, or microRNA-300 knockdown could enhance the migratory and invasive capacities, as well as increase EMT ofBT549 cells. On the contrary, knockdown of DLEU1 or RAB22A, or microRNA-300 overexpression in MCF-7 cells obtained the opposite trends of cellular behaviors. Dual-luciferase reporter gene assay confirmed that DLEU1 and RAB22A could bind to microRNA-300. Further verification showed that RAB22A expression was positively regulated by DLEU1, but negatively regulated by microRNA-300. Finally, we found that DLEU1 overexpression could reverse the inhibitory effects of microRNA-300 on proliferation, migration, and EMT of breast cancer cells.

CONCLUSIONS: DLEU1 is highly expressed in breast cancer, which promotes migration, invasion, and EMT of breast cancer cells by targeting microRNA-300 to mediate RAB22A.

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