Yichang Yiling People's Hospital, Yichang, Hubei, China.
Ultrasound Q. 2024 Jun 1;40(2):136-143. doi: 10.1097/RUQ.0000000000000678.
Ultrasound-targeted microbubble destruction (UTMD) technology combines ultrasound with a variety of functional microbubble vectors to enhance the transfection and expression of target genes, and has become a promising noninvasive method for localized gene transfer, which is widely used in gene therapy for cancer. This research aimed to explore the role of UTMD-mediated miR-145-5p on breast cancer (BC) tumorigenesis and the underlying mechanisms. To achieve UTMD-mediated miR-145-5p overexpression, BC cells were cotransfected with microbubbles (MBs) and miR-145-5p mimics. The BC cell malignant phenotypes were assessed through CCK-8, wound healing, and transwell assays. MiR-145-5p and actin gamma 1 (ACTG1) binding relationship was verified through luciferase reporter and RNA pull-down assays. MiR-145-5p and ACTG1 levels in BC cells and tissues were detected through RT-qPCR and Western blotting. ACTG1 was upregulated, whereas miR-145-5p was downregulated in BC cells and tissues. MiR-145-5p targeted ACTG1 and negatively regulated its level in BC cells. Overexpressing miR-145-5p restrained BC cell growth, migration, and invasion. Ultrasound-targeted microbubble destruction improved the overexpression efficiency of miR-145-5p and enhanced the suppressive influence on BC cell malignant phenotypes. In addition, ACTG1 overexpression compromises the repression of UTMD-mediated miR-145-5p on cellular behaviors in BC. Ultrasound-targeted microbubble destruction-delivered miR-145-5p hindered malignant behaviors of BC cells through downregulating ACTG1.
超声靶向微泡破坏（UTMD）技术结合了超声与多种功能微泡载体，以增强靶基因的转染和表达，已成为局部基因转移的一种有前途的非侵入性方法，广泛应用于癌症的基因治疗。本研究旨在探讨 UTMD 介导的 miR-145-5p 对乳腺癌（BC）肿瘤发生的作用及其潜在机制。为了实现 UTMD 介导的 miR-145-5p 过表达，将微泡（MBs）和 miR-145-5p 模拟物共转染至 BC 细胞。通过 CCK-8、划痕愈合和 Transwell 实验评估 BC 细胞的恶性表型。通过荧光素酶报告和 RNA 下拉实验验证 miR-145-5p 和肌动蛋白γ 1（ACTG1）的结合关系。通过 RT-qPCR 和 Western blot 检测 BC 细胞和组织中的 miR-145-5p 和 ACTG1 水平。miR-145-5p 在 BC 细胞和组织中下调，而 ACTG1 上调。miR-145-5p 靶向 ACTG1 并负调控其在 BC 细胞中的水平。过表达 miR-145-5p 抑制 BC 细胞的生长、迁移和侵袭。超声靶向微泡破坏提高了 miR-145-5p 的过表达效率，并增强了对 BC 细胞恶性表型的抑制作用。此外，ACTG1 的过表达损害了 UTMD 介导的 miR-145-5p 对 BC 细胞行为的抑制作用。超声靶向微泡破坏递送的 miR-145-5p 通过下调 ACTG1 抑制 BC 细胞的恶性行为。
