Department of Breast Surgery, Peking Union Medical College Hospital (PUMCH), Dongcheng, Beijing 100730, P.R. China.
Department of Breast Surgery, Peking Union Medical College Hospital (PUMCH), Dongcheng, Beijing 100730, P.R. China.
Oncol Rep. 2018 Aug;40(2):849-858. doi: 10.3892/or.2018.6517. Epub 2018 Jun 20.
The present study was performed to investigate the biological functions of microRNA‑320a in human breast cancer and the underlying mechanisms. MicroRNA‑320a expression was downregulated in human breast cancer, compared with the normal control. Overexpression of microRNA‑320a induced apoptosis, and inhibited cell viability and invasion in MDA‑MB‑231cells while downregulation of microRNA‑320a reduced apoptosis, and increased cell viability and invasion in MDA‑MB‑231 cells. Then, overexpression of microRNA‑320a suppressed insulin‑like growth factor 1 receptor (IGF‑1R), p‑AKt and cyclin D1 protein expression in MDA‑MB‑231cells. In addition, the downregulation of microRNA‑320a induced IGF‑1R, p‑Akt and cyclin D1 protein expression in MDA‑MB‑231cells. Furthermore, the IGF‑1R inhibitor increased the effects of microRNA‑320a on the apoptosis of MDA‑MB‑231 cells. The p‑Akt inhibitor (MK 2206 dihydrochloride, 2.5 nM) increased the effects of microRNA‑320a on the apoptosis of MDA‑MB‑231 cells. These results revealed that microRNA‑320a suppresses tumor cell growth and invasion of human breast cancer by targeting IGF‑1R.
本研究旨在探讨 microRNA-320a 在人乳腺癌中的生物学功能及其潜在机制。与正常对照相比,人乳腺癌中 microRNA-320a 的表达下调。过表达 microRNA-320a 可诱导 MDA-MB-231 细胞凋亡,并抑制细胞活力和侵袭能力,而下调 microRNA-320a 则减少细胞凋亡,并增加 MDA-MB-231 细胞的活力和侵袭能力。过表达 microRNA-320a 还可抑制 MDA-MB-231 细胞中胰岛素样生长因子 1 受体(IGF-1R)、磷酸化 AKt 和细胞周期蛋白 D1 蛋白的表达。此外,下调 microRNA-320a 可诱导 MDA-MB-231 细胞中 IGF-1R、磷酸化 AKt 和细胞周期蛋白 D1 蛋白的表达。此外,IGF-1R 抑制剂可增强 microRNA-320a 对 MDA-MB-231 细胞凋亡的影响。AKt 抑制剂(MK 2206 二盐酸盐,2.5 nM)可增强 microRNA-320a 对 MDA-MB-231 细胞凋亡的影响。这些结果表明,microRNA-320a 通过靶向 IGF-1R 抑制人乳腺癌肿瘤细胞的生长和侵袭。