Neurosurgery Institute, Key Laboratory on Brain Function Repair and Regeneration of Guangdong, Zhujiang Hospital of Southern Medical University, Guangzhou 510282, China.
Biochem Biophys Res Commun. 2013 Jun 14;435(4):745-50. doi: 10.1016/j.bbrc.2013.05.056. Epub 2013 May 23.
microRNAs have been demonstrated to play important roles in cancer development and progression. Hence, identifying functional microRNAs and better understanding of the underlying molecular mechanisms would provide new clues for the development of targeted cancer therapies. Herein, we reported that a microRNA, miR-421 played an oncogenic role in nasopharyngeal carcinoma. Upregulation of miR-421 induced, whereas inhibition of miR-421 repressed cell proliferation and apoptosis resistance. Furthermore, we found that upregulation of miR-421 inhibited forkhead box protein O4 (FOXO4) signaling pathway following downregulation of p21, p27, Bim and FASL expression by directly targeting FOXO4 3'UTR. Additionally, we demonstrated that FOXO4 expression is critical for miR-421-induced cell growth and apoptosis resistance. Taken together, our findings not only suggest that miR-421 promotes nasopharyngeal carcinoma cell proliferation and anti-apoptosis, but also uncover a novel regulatory mechanism for inactivation of FOXO4 in nasopharyngeal carcinoma.
microRNAs 在癌症的发生和发展中起着重要作用。因此，鉴定功能性 microRNAs 并更好地理解潜在的分子机制将为开发靶向癌症治疗提供新的线索。本文报道了 microRNA-421 在鼻咽癌中发挥致癌作用。miR-421 的上调诱导细胞增殖和抗凋亡，而 miR-421 的抑制则抑制细胞增殖和抗凋亡。此外，我们发现上调 miR-421 通过直接靶向 FOXO4 3'UTR 抑制 FOXO4 信号通路，从而下调 p21、p27、Bim 和 FASL 的表达。此外，我们证明了 FOXO4 的表达对于 miR-421 诱导的细胞生长和抗凋亡是至关重要的。总之，我们的研究结果不仅表明 miR-421 促进鼻咽癌细胞的增殖和抗凋亡，而且揭示了鼻咽癌中 FOXO4 失活的新的调控机制。
