Long non-coding RNA DARS-AS1 facilitates breast cancer progression by modulating the miR-6835-3p/ATF3 axis

Abstract

Long non-coding RNAs (lncRNAs) play crucial roles in various cellular processes associated with cancer progression, including invasion, proliferation, and metastasis. Despite this understanding, the specific role of DARS-AS1 in breast cancer remains underexplored. In this study, we employed quantitative reverse transcription-polymerase chain reaction to measure the expression levels of DARS-AS1 and miR-6835-3p. Functional assessments, including the cell invasion and CCK-8 assays, were conducted to investigate cellular behaviors. In addition, a luciferase reporter assay was employed to elucidate the mechanistic interaction between DARS-AS1 and miR-6835-3p. Notably, DARS-AS1 expression was elevated in breast cancer cell lines (MCF7 and MDA-MB-231) relative to the non-cancerous MCF-10A cells. Overexpression of DARS-AS1 enhanced cell growth and invasion in MDA-MB-231 breast cancer cells. Further investigation revealed that DARS-AS1 acts as a sponge for miR-6835-3p in breast cancer cells. Overexpression of miR-6835-3p inhibited luciferase activity, specifically in the presence of wild-type DARS-AS1, highlighting a direct interaction. Ectopic expression of DARS-AS1 suppressed miR-6835-3p in MDA-MB-231 cells. Concurrently, miR-6835-3p levels were downregulated in breast cancer cells, and miR-6835-3p exhibited a negative correlation with DARS-AS1 expression. Mechanistically, miR-6835-3p targeted ATF3 expression in breast cancer cells. Increased levels of DARS-AS1 were found to enhance cellular proliferation and invasion by modulating ATF3. Our findings indicate that DARS-AS1 acts as an oncogene in breast cancer, partially through regulation of the miR-6835-3p/ATF3 pathway. This study provides valuable insights into the molecular mechanisms contributing to breast cancer progression, offering potential targets for therapeutic interventions.