Department of Thyroid and Breast Surgery, Xian Yang Central Hospital, Xianyang, Shanxi, China.
Anticancer Drugs. 2022 Jan 1;33(1):e700-e710. doi: 10.1097/CAD.0000000000001243.
Breast cancer is a frequent tumor threatening the health of women. Circular RNAs (circRNAs) play vital roles in cancer progression and chemoresistance. Herein, we mainly investigate the role and potential mechanism of circRNA ataxin 7 (circATXN7; circ_0066436) in breast cancer. RNA expression levels were detected via quantitative real-time PCR (qPCR), western blot and immunohistochemistry. Cell viability and half inhibitory concentration (IC50) of doxorubicin were assessed by cell counting kit-8 (CCK-8) method. Cell proliferation, migration and invasion were determined by CCK-8, 5-ethynyl-2'-deoxyuridine, colony formation and transwell assays. The binding relationship between microRNA-149-5p (miR-149-5p) and circATXN7 or homeobox A11 (HOXA11) was validated via dual-luciferase reporter assay and RNA immunoprecipitation assay. Xenograft assay was conducted to analyze the effect of circATXN7 on doxorubicin resistance of breast cancer. CircATXN7 and HOXA11 levels were enhanced, whereas miR-149-5p level was declined in breast cancer tissues and cells. CircATXN7 silencing suppressed breast cancer development and doxorubicin resistance. Additionally, circATXN7 upregulated HOXA11 via absorbing miR-149-5p, thereby inducing breast cancer cell progression and reducing doxorubicin sensitivity. Besides, depletion of circATXN7 enhanced doxorubicin sensitivity in vivo. Interference of circATXN7 inhibited breast cancer progression and doxorubicin resistance via mediating miR-149-5p/HOXA11 axis, which might provide a possible biomarker for breast cancer therapy.
乳腺癌是一种常见的威胁女性健康的肿瘤。环状 RNA（circRNAs）在癌症进展和化疗耐药中发挥重要作用。在此，我们主要研究环状 RNA 共济失调 7（circATXN7; circ_0066436）在乳腺癌中的作用和潜在机制。通过实时定量 PCR（qPCR）、western blot 和免疫组织化学检测 RNA 表达水平。通过细胞计数试剂盒-8（CCK-8）法评估细胞活力和阿霉素的半抑制浓度（IC50）。通过 CCK-8、5-乙炔基-2'-脱氧尿苷、集落形成和 Transwell 测定法测定细胞增殖、迁移和侵袭。通过双荧光素酶报告基因检测和 RNA 免疫沉淀测定验证 microRNA-149-5p（miR-149-5p）与 circATXN7 或同源盒 A11（HOXA11）之间的结合关系。通过异种移植实验分析 circATXN7 对乳腺癌阿霉素耐药性的影响。在乳腺癌组织和细胞中，circATXN7 和 HOXA11 水平升高，而 miR-149-5p 水平降低。circATXN7 沉默抑制乳腺癌的发展和阿霉素耐药性。此外，circATXN7 通过吸收 miR-149-5p 上调 HOXA11，从而诱导乳腺癌细胞进展并降低阿霉素敏感性。此外，circATXN7 的耗竭增强了体内阿霉素的敏感性。干扰 circATXN7 通过调节 miR-149-5p/HOXA11 轴抑制乳腺癌进展和阿霉素耐药性，这可能为乳腺癌治疗提供一个潜在的生物标志物。
