Background: Breast cancer is the most commonly diagnosed cancer in women. Triple negative breast cancer (TNBC) is the most difficult subtype of breast cancer to treat due to the deficiency in drug-targetable receptors. LRP11-AS1, a newly identified oncogenic long noncoding RNA (lncRNA) was found to be significantly overexpressed in TNBC cells. The aim of this study is to investigate the malignant roles and the oncogenic mechanisms of LRP11-AS1 in TNBC.
Methods: CCK-8, colony formation, transwell migration and transwell invasion assays were performed to study the functions of LRP11-AS1. Quantitative PCR and western blot were used to determine the gene expression. Bioinformatics analysis and dual-luciferase reporter assay were conducted to study lncRNA and miRNA interactions.
Results: LRP11-AS1 was found to be significantly overexpressed in TNBC cells compared to the non-TNBC cells and normal mammary epithelial cells. Knockdown of LRP11-AS1 could inhibit the growth and metastasis of TNBC cells and regulate cell cycle. Mechanistically, LRP11-AS1 was found to act as a competing endogenous RNA (ceRNA) to sponge miR-149-3p. Silencing of LRP11-AS1 increased the expression of miR-149-3p and overexpression of miR-149-3p suppressed the expression of LRP11-AS1. Inhibition of miR-149-3p could reverse the anticancer effect of LRP11-AS1 deficiency in TNBC cells. Moreover, Neuropilin-2 (NRP2) was found to be the target of miR-149-3p. Rescue experiments revealed that NRP2 overexpression could rescue the anticancer effect of LRP11-AS1 deficiency in TNBC cells.
Conclusion: LRP11-AS1 overexpressed in TNBC showed the oncogenic effects possibly by sponging miR-149-3p and regulating the miR-1493p/NRP2 axis, which indicated LRP11-AS1 as a potential diagnostic biomarker and therapeutic target in TNBC.