LncRNA DSCAM-AS1 acts as a sponge of miR-137 to enhance Tamoxifen resistance in breast cancer.

ABSTRACT

OBJECTIVE: To investigate the influence of long noncoding RNA (lncRNA) DSCAM-AS1 on the propagation and apoptosis of Tamoxifen-resistant (TR) breast cancer cells via regulation of mircoRNA (miR)-137 and epidermal growth factor receptor pathway substrate 8 (EPS8). METHODS: Data of GSE5840 downloaded from the Gene Expression Omnibus database were utilized to screen out aberrantly expressed lncRNA and messenger RNA in breast cancer tissue samples. The expressions of DSCAM-AS1, miR-137, and EPS8 were determined by quantitative real time polymerase chain reaction (qRT-PCR). Cell lines were screened by half maximal inhibitory concentration (IC 50 ). 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay and the flow cytometry assay were used to detect cell proliferation, apoptosis, and cell cycle. The relationship among DSCAM-AS1, miR-137, and EPS8 was studied by miRcode, TargetScan, and Pearson correlation coefficient. A xenograft mouse model experiment was performed to demonstrate the effect of DSCAM-AS1 and EPS8 on tumor growth in vivo. RESULTS: LncRNA DSCAM-AS1 and EPS8 were significantly upregulated, whereas miR-137 was downregulated in TR tissues. DSCAM-AS1 could promote the Tamoxifen resistance of breast cancer, and it was negatively correlated with miR-137, whereas positively correlated with the expression of EPS8 in TR breast cancer tissues. Furthermore, miR-137 could inhibit tumor development and arrest cell cycle at the G0/G1 phase by targeting the 3'-UTR of EPS8. DSCAM-AS1 targeted miR-137 and EPS8 to promote propagation of TR breast cancer cells and inhibit cell apoptosis. CONCLUSION: LncRNA DSCAM-AS1 acts as a competing endogenous RNA of miR-137 and regulates EPS8 to promote cell reproduction and suppresses cell apoptosis in TR breast cancer.