Department of Breast Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Bioengineered. 2022 Feb;13(2):3896-3910. doi: 10.1080/21655979.2022.2031384.
SOCS3 is low-expressed in breast cancer and may be a potential target. Ultrasound targeted microbubble destruction (UTMD) improved the efficiency of gene transfection. We explored the effects of UTMD-mediated transfection of SOCS3 on the biological characteristics and epithelial-mesenchymal transition (EMT) of breast cancer stem cells (BCSCs). The expression of SOCS3 in breast cancer (BC) and its association with prognosis were evaluated by GEPIA and The Cancer Genome Atlas (TCGA) websites. BCSCs were sorted by flow cytometry and immunomagnetic bead method, followed by sphere formation, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and xenograft assays to test their effects and . The levels of SOCS3, EMT- and STAT3 pathway-related genes were determined by RT-qPCR and Western blot, respectively. The effects of liposome and UTMD on BCSCs and mice were compared by the gain-of-function experiments. Low expression of SOCS3 was associated with poor prognosis of BC patients, and found in BC and BCSCs. BCSCs were successfully sorted, with high viability and tumorigenicity. UTMD increased the transfection rate of SOCS3. Moreover, UTMD- and liposome-mediated SOCS3 reduced cell viability, proliferation, migration and invasion, blocked cell cycle, inhibited sphere formation in BCSCs, and retarded tumor growth in mice. Mechanistically, overexpressed SOCS3 inhibited the expressions of EMT-related genes and the activation of STAT3 pathway in BCSCs and mice. The regulatory effects of UTMD-mediated SOCS3 on the above-mentioned biological characteristics were better than liposome-mediated SOCS3. UTMD-mediated SOCS3 has a better therapeutic effect in BC, providing new experimental evidence for the treatment of BC.
SOCS3 在乳腺癌中低表达，可能是一个潜在的靶点。超声靶向微泡破坏（UTMD）提高了基因转染的效率。我们探讨了 UTMD 介导的 SOCS3 转染对乳腺癌干细胞（BCSCs）的生物学特性和上皮-间充质转化（EMT）的影响。通过 GEPIA 和癌症基因组图谱（TCGA）网站评估 SOCS3 在乳腺癌（BC）中的表达及其与预后的关系。采用流式细胞术和免疫磁珠法分选 BCSCs，然后进行球体形成、3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐（MTT）和异种移植实验，以检测其作用。通过 RT-qPCR 和 Western blot 分别测定 SOCS3、EMT 和 STAT3 通路相关基因的水平。通过功能获得实验比较脂质体和 UTMD 对 BCSCs 和小鼠的影响。SOCS3 的低表达与 BC 患者的不良预后相关，并且在 BC 和 BCSCs 中均发现。BCSCs 成功分离，具有较高的活力和致瘤性。UTMD 增加了 SOCS3 的转染率。此外，UTMD 和脂质体介导的 SOCS3 降低了 BCSCs 的细胞活力、增殖、迁移和侵袭，阻断了细胞周期，抑制了 BCSCs 的球体形成，并减缓了小鼠肿瘤的生长。机制上，过表达的 SOCS3 抑制了 EMT 相关基因在 BCSCs 和小鼠中的表达以及 STAT3 通路的激活。UTMD 介导的 SOCS3 对上述生物学特性的调节作用优于脂质体介导的 SOCS3。UTMD 介导的 SOCS3 在 BC 中具有更好的治疗效果，为 BC 的治疗提供了新的实验证据。
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