Department of Physiology, School of Basic Medical Sciences, Jinzhou Medical University, Jinzhou, Liaoning, 121001, People's Republic of China.
Biological Anthropology Institute, Jinzhou Medical University, Jinzhou, Liaoning, 121001, People's Republic of China; Key Laboratory of Chinese Physical Characteristics Research of Liaoning Province, Jinzhou Medical University, Jinzhou, Liaoning, 121001, People's Republic of China.
Exp Cell Res. 2020 May 1;390(1):111939. doi: 10.1016/j.yexcr.2020.111939. Epub 2020 Mar 4.
MiR-328-3p has been reported to be downregulated and serve as a tumor suppressor in several cancers. Previous studies only have reported the downregulation of miR-328-3p in CRC. However, the roles of miR-328-3p in CRC growth and metastasis were unknown. In this study, we demonstrated that miR-328-3p overexpression inhibited cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT). The PI3K/Akt signaling pathway was also inactivated by miR-328-3p overexpression. MiR-328-3p knockdown showed the opposite effects. In addition, we confirmed that miR-328-3p directly bound to 3'UTR of Girdin and negatively regulated its expression. Girdin knockdown or treatment with PI3K inhibitor LY294002 blocked the effects of miR-328-3p inhibitor on cell proliferation, metastasis, and the PI3K/Akt signaling pathway. Moreover, pre-miR-328 decreased numbers of liver metastatic nodules, and reduced the levels of p-Akt, p-Girdin, and Girdin in metastatic tissues in liver. In conclusion, miR-328-3p may inhibit proliferation and metastasis of CRC cells by targeting Girdin and inactivating the PI3K/Akt signaling pathway. MiR-328-3p may be a novel target in cancer therapy.
miR-328-3p 已被报道在多种癌症中下调并作为肿瘤抑制因子发挥作用。先前的研究仅报道了 miR-328-3p 在 CRC 中的下调。然而,miR-328-3p 在 CRC 生长和转移中的作用尚不清楚。在本研究中,我们证明 miR-328-3p 的过表达抑制了细胞增殖、迁移、侵袭和上皮-间充质转化(EMT)。PI3K/Akt 信号通路也被 miR-328-3p 的过表达所抑制。miR-328-3p 的敲低则表现出相反的效果。此外,我们证实 miR-328-3p 直接结合 Girdin 的 3'UTR,并负调控其表达。Girdin 的敲低或 PI3K 抑制剂 LY294002 的处理阻断了 miR-328-3p 抑制剂对细胞增殖、转移和 PI3K/Akt 信号通路的影响。此外,pre-miR-328 减少了肝转移结节的数量,并降低了转移性组织中 p-Akt、p-Girdin 和 Girdin 的水平。总之,miR-328-3p 可能通过靶向 Girdin 并抑制 PI3K/Akt 信号通路来抑制 CRC 细胞的增殖和转移。miR-328-3p 可能成为癌症治疗的新靶点。