Expression of LINC00461 in breast cancer cells and its modulatory effect on miR-607/SLCLA3 axis

Abstract

Purpose: To investigate the role and mechanisms of action of long non-coding RNA (lncRNA) (LINC00461) in breast cancer. 
 Methods: Human breast cancer cell lines and normal mammary epithelial cell lines as well as their corresponding negative controls (NC) were cultured and co-transfected with Lipofectamine 3000. Expressions of LINC00461 and miR-607 were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR), while the SLC1A3 level was evaluated by western blot. The role of LINC00461 in cell proliferation, apoptosis, cycle arrest, glycolysis, and chemoresistance was determined by MTT, colony formation, flow cytometry, and ELISA assays. 
 Results: The LINC00461 level was overexpressed in breast cancer cell lines (p ˂ 0.05). Knockdown of LINC00461 in MCF-7 cells inhibited cell viability (p ˂ 0.01) and the degree of colony formation (p ˂ 0.001), induced cell apoptosis (p ˂ 0.001) and cycle arrest (p ˂ 0.01), and suppressed glucose consumption (p ˂ 0.001), lactate production (p ˂ 0.001), LDHA activity (p ˂ 0.05) and cisplatin sensitivity (p ˂ 0.05). Overexpression of LINC00461 in MDA-MB-468 cells resulted in reverse outcomes. LINC00461 positively regulated the expression of SLC1A3 via miR-607 in breast cancer cells. It was mechanistically established that LINC00461 is bound to miR-607 and miR-607 bound to SLC1A3, and this was confirmed by luciferase assay. 
 Conclusion: LINC00461 induces cell proliferation, cycle arrest, glycolysis, and chemoresistance by modulating miR-607/SLC1A3 axis in breast cancer. The results lay the theoretical basis for monitoring and therapy of breast cancer.