Purpose: Breast cancer (BC) is the most common malignant cancer in women worldwide. Recently, long non-coding RNAs (LncRNAs) have been reported to have essential roles in BC tumorigenesis.
Patients and Methods: Tumor and adjacent non-tumor tissue samples were collected from patients with BC (n = 168) for comparison of LncRNA and miRNA expression levels. Patient clinical, demographic, and molecular data were analyzed by univariate and multivariate methods to identify factors associated with patient survival, and a nomogram was generated using significant risk/protective factors. Further, analyses of LINC00461  and miR-411-5p expression and function were conducted in BC and normal breast epithelial cell lines, by quantitative RT-PCR, cell proliferation, wound-healing, RNA pull-down, RNA immunoprecipitation, and luciferase assays. Docetaxel (DTX)-resistant BC cell lines were also generated and used to assess the roles of LINC00461  and miR-411-5p in drug resistance.
Results: LINC00461  was up-regulated in BC tissues relative to adjacent non-tumor samples, and expression of LINC00461  was correlated with poor patient prognosis. LINC00461  knockdown could inhibit proliferation of BC cells in vitro. Further, LINC00461  expression was higher in DTX-resistant than in non-resistant BC cell lines. Our data support a role for LINC00461  as a competitive endogenous RNA sponge involved in regulation of miR-411-5p expression in BC. miR-411-5p was down-regulated in both BC tissues and cell lines, with levels negatively correlated with those of LINC00461 . Moreover, miR-411-5p was down-regulated in DTX-resistant BC cell lines compared with non-resistant cell lines.
Conclusion: In conclusion, LINC00461  promotes proliferation, migration, and DTX-resistance in BC by acting as a sponge for miR-411-5p. This process represents a potential therapeutic target for patients with BC.
Keywords: lncRNA, miRNA, proliferation, migration, ceRNA