Key Laboratory of Integrative Chinese and Western Medicine for the Diagnosis and Treatment of Circulatory Diseases of Zhejiang Province, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, P.R. China.
Department of Breast Surgery, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, P.R. China.
Immunopharmacol Immunotoxicol. 2022 Aug;44(4):492-499. doi: 10.1080/08923973.2022.2054428. Epub 2022 Mar 25.
Doxorubicin (DOX) resistance remains a major challenge for adriamycin-based treatment of breast cancer (BC). Transforming growth factor β (TGF-β) 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-β-induced resistance remains limited. This study aimed to investigate the role of LncRNA on the regulation of TGF-β-induced drug resistance.
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.
TGF-β induced EMT and promoted DOX resistance. LncRNA urothelial carcinoma-associated 1(lncRNA UCA1) associated with TGF-β 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-β on EMT and DOX resistance disappeared following a lncRNA UCA1 knockdown.
These findings suggest that lncRNA-UCA1, a mediator of TGF-β signaling, could predispose BC patients to EMT and DOX resistance.
多柔比星（DOX）耐药仍然是阿霉素为基础的乳腺癌（BC）治疗的主要挑战。转化生长因子β（TGF-β）已被报道有助于耐药。尽管长链非编码 RNA（LncRNA）在癌症进展中的作用已被广泛研究，但它对 TGF-β诱导的耐药性的影响仍然有限。本研究旨在探讨 LncRNA 在调节 TGF-β诱导的耐药性中的作用。
使用细胞计数试剂盒-8（CCK-8）和 EdU 测定法评估细胞活力和增殖。通过定量实时 PCR 检测 BC 组织和细胞中 LncRNA mRNA 的表达水平。通过 Western blot 和免疫荧光定量上皮-间充质转化（EMT）和细胞凋亡的变化。
TGF-β诱导 EMT 并促进 DOX 耐药。LncRNA 膀胱癌相关 1（lncRNA UCA1）与 TGF-β 相关，在 BC 细胞和组织中上调。沉默 lncRNA UCA1 可增强 DOX 敏感性，降低 BC 细胞的增殖并增加细胞凋亡。TGF-β 对 EMT 和 DOX 耐药性的影响在 lncRNA UCA1 敲低后消失。
这些发现表明，作为 TGF-β 信号的中介，lncRNA-UCA1 可能使 BC 患者易发生 EMT 和 DOX 耐药性。
