Up-regulation of LncRNA UCA1 by TGF-beta promotes doxorubicin resistance in breast cancer cells

Background: Doxorubicin (DOX) resistance remains a major challenge for adriamycin-based treatment of breast cancer (BC). Transforming growth factor beta (TGF-beta) has been reported to contribute to drug resistance. Although the role of long noncoding RNAs (LncRNAs) in cancer progression has been widely studied, its effect on TGF-beta-induced resistance remains limited. This study aimed to investigate the role of LncRNA on the regulation of TGF-beta-induced drug resistance. Methods: Cell counting kit-8 (CCK-8) and an EdU assay were used to evaluate cell viability and proliferation. The level of LncRNA mRNA expression in BC tissues and cells was examined by quantitative real-time PCR. Changes in epithelial-mesenchymal transition (EMT) and cell apoptosis were quantified by Western blot and immunofluorescence. Results: TGF-beta induced EMT and promoted DOX resistance. LncRNA urothelial carcinoma-associated 1(lncRNA UCA1) associated with TGF-beta was upregulated in BC cells and tissues. LncRNA UCA1 silencing enhanced sensitivity to DOX decreased cellular proliferation and increased apoptosis in BC cells. The effect of TGF-beta on EMT and DOX resistance disappeared following a lncRNA UCA1 knockdown. Conclusions: These findings suggest that lncRNA-UCA1, a mediator of TGF-beta signaling, could predispose BC patients to EMT and DOX resistance.