Long non-coding RNA LINC01559 serves as a competing endogenous RNA accelerating triple-negative breast cancer progression

Abstract

Background: Long non-coding RNA (lncRNA) is an endogenous RNA over 200 nt in length involved in gene regulation. LINC01559 is a novel lncRNA that has been identified as a fundamental player in human cancer. However, its role in triple-negative breast cancer (TNBC) remains unknown. Here, we explored the expression, function and clinical implication of LINC01559 in TNBC. Methods: RNA expression was detected by qRT-PCR analysis. Cell Counting Kit-8 (CCK-8), 5-Ethynyl-2′-deoxyuridine (EdU), wound healing and Transwell assays were used to test cell viability, DNA synthesis rate, migration and invasion, respectively. The competing endogenous RNA (ceRNA) axis involved in LINC01559 was determined by RNA pull-down and luciferase reporter assays. The xenograft model was used to verify the function of LINC01559 in vivo. Results: LINC01559 was significantly increased in TNBC tissues as compared to matched normal tissues, which was due to high levels of H3K4Me3 and H3K27Ac in the promoter region. Knockdown of LINC01559 inhibited TNBC cell proliferation, migration and invasion in vitro, and also retarded tumor growth and reduced lung metastasis in vivo. Mechanistically, LINC01559 served as a ceRNA that sponged miR-370-3p, miR-485-5p and miR-940, resulting in increasing the expression of a cohort of oncogenes, thus accelerating TNBC progression. Conclusions: Our data provide a comprehensive analysis of LINC01559 in TNBC, we found that LINC01559 functioned as a carcinogenic ceRNA via sponging miRNAs. Targeting of LINC01559 may be a potential treatment for TNBC patients.

Keywords

• LncRNA
• LINC01559
• ceRNA
• TNBC
• Histone modification