Department of Breast Surgery, Yantaishan Hospital, Yantai, China.
Eur Rev Med Pharmacol Sci. 2019 Feb;23(3):1151-1157. doi: 10.26355/eurrev_201902_17006.
The aim of this study was to investigate the influence of micro ribonucleic acid (miR)-34a on resistance to sunitinib in breast cancer, and to explore its possible underlying mechanism.
Breast cancer MCF-7 cells were transfected with miR-34a inhibitor or mimics to downregulate or upregulate the expression of miR-34a. Then, the transfected cells were treated with sunitinib. Next, transwell assay was applied to detect the changes in cell invasion ability. Cell viability was measured via cell counting kit-8 (CCK8) assay. Dual-Luciferase reporter gene assay was employed to determine the interaction between miR-34a and the Wnt/β-catenin signaling pathway. The immunoblotting assay was used to measure the expression changes of proteins in the pathway.
The overexpression of miR-34a significantly reduced the invasive ability of MCF-7 cells after treatment with sunitinib. After miR-34a expression was downregulated, the sensitivity of MCF-7 cells to sunitinib was significantly lowered. MiR-34a interacted with the 3'-untranslated region (3'-UTR) on Wnt1. Meanwhile, the overexpression of miR-34a remarkably downregulated the messenger RNA (mRNA) and the protein levels of Wnt1, whereas upregulated the expressions of Wnt1 and β-catenin.
MiR-34a affects the sensitivity to sunitinib in breast cancer by regulating the Wnt/β-catenin signaling pathway.
本研究旨在探讨微小 RNA-34a（miR-34a）对乳腺癌对舒尼替尼耐药性的影响，并探讨其可能的作用机制。
用 miR-34a 抑制剂或模拟物转染乳腺癌 MCF-7 细胞，下调或上调 miR-34a 的表达。然后，用舒尼替尼处理转染的细胞。接下来，采用 Transwell 小室实验检测细胞侵袭能力的变化。通过细胞计数试剂盒-8（CCK8）法测量细胞活力。采用双荧光素酶报告基因实验确定 miR-34a 与 Wnt/β-连环蛋白信号通路的相互作用。采用免疫印迹法检测该通路中蛋白的表达变化。
miR-34a 的过表达可显著降低舒尼替尼处理后的 MCF-7 细胞的侵袭能力。下调 miR-34a 的表达后，MCF-7 细胞对舒尼替尼的敏感性显著降低。miR-34a 与 Wnt1 的 3'-非翻译区（3'-UTR）相互作用。同时，miR-34a 的过表达显著下调 Wnt1 的信使 RNA（mRNA）和蛋白水平，而上调 Wnt1 和 β-连环蛋白的表达。
miR-34a 通过调节 Wnt/β-连环蛋白信号通路影响乳腺癌对舒尼替尼的敏感性。
