Abstract / Summary
Abstract Adriamycin resistance is closely associated with treatment failure and poor prognosis in breast cancer. Here, we show that C1RL-AS1 is down-regulated by Adriamycin and is associated with better prognosis in patients with luminal A breast cancer. C1RL-AS1 overexpression restored Adriamycin sensitivity in resistant breast cancer cells and suppressed tumor growth in a xenograft mouse model. Mechanistically, Adriamycin reduced H3K27 acetylation at the C1RL-AS1 promoter, thereby inhibiting C1RL-AS1 transcription. Luciferase reporter and RNA pull-down assays confirmed that C1RL-AS1 directly interacts with miR-3150a-3p, which is up-regulated in Adriamycin-resistant cells. miR-3150a-3p knockdown sensitized resistant cells to Adriamycin and inhibited cell viability. By sponging miR-3150a-3p, C1RL-AS1 released IFNAR2 expression and activated JAK1/STAT1 signaling, promoting PD-L1 transcription. Lower IFNAR2 expression was associated with reduced immune cell infiltration in breast cancer patients. These findings suggest that Adriamycin-silenced C1RL-AS1 may be a potential therapeutic target for overcoming chemotherapy resistance in breast cancer.