Long noncoding RNA LINC00511 involves in breast cancer recurrence and radioresistance by regulating STXBP4 expression via miR-185

摘要

OBJECTIVE: The aim of this study was to explore the molecular function of long intergenic noncoding RNA 00511 (LINC00511) and its target proteins in recurrent breast cancer after breast-conserving surgery followed by radiotherapy. PATIENTS AND METHODS: LINC00511 expression in tissues was measured by quantitative polymerase chain reaction (qPCR). The association between LINC00511 expression and the clinicopathological features of breast cancer was analyzed by Chi-square tests. The impact of LINC00511 on overall survival was evaluated by the log-rank test. MDA-MB-231/MDA-MB-436 cell lines transfected with short hairpin RNA (shRNA) were used to investigate the influence of LINC00511 silencing on tumor growth and radiosensitivity in vitro and in vivo. A series of experiments including cell apoptosis assay, cell colony formation assay, and mouse xenograft models were applied to test those transfected cell lines. MicroRNA (miRNA) targets of LINC00511 were identified by bioinformatics analysis and further validated by dual luciferase reporter assay, qPCR, and Western blot analysis. RESULTS: LINC00511 expression was significantly increased in breast cancer tissues and correlated with recurrence and poor survival after breast-conserving surgery followed by radiotherapy. LINC00511 knockdown by shRNA restricted cell proliferation, promoted cell apoptosis, and enhanced radiosensitivity in vitro, and inhibited tumor growth with an increased response to radiation in vivo. In addition, elevated LINC00511 was found to increase syntaxin-binding protein 4 (STXBP4) expression through competitive binding to miR‐185, while silencing LINC00511 decreased STXBP4 expression and increased radiosensitivity. CONCLUSIONS: LINC00511 inhibition impairs its competitive binding to miR‐185, resulting in increased STXBP4 expression and improved radiation response in breast cancer. Our study results suggest that the LINC00511/miR-185/STXBP4 axis may be a promising therapeutic target for improving the prognosis of breast cancer.