Li Yu, Li Wei, Zhang Jian-Guo, Li Hai-Yang, Li Yong-Ming
Department of Neurosurgery, Henan Provincial People's Hospital, Zhengzhou University, Henan, 450003, China,
Tumour Biol. 2014 Oct;35(10):10011-7. doi: 10.1007/s13277-014-1921-1. Epub 2014 Jul 11.
Neuroblastoma, featured by a high rate of spontaneous remissions, is the most common extra-cranial solid tumor in infants and children. Numerous reports have demonstrated that MicroRNAs (miRNAs) play essential roles in cancer progression, including cell proliferation, apoptosis, invasion, metastasis and angiogenesis. miR-421 functions as an onco-miR in some malignancies. However, its role in neuroblastoma remains poorly understood. In the present study, we found that miR-421 was increased in neuroblastoma tissues compared with matched adjacent normal tissues. Forced overexpression of miR-421 substantially enhanced cell proliferation, cell-cycle progression, migration, and invasion of neuroblastoma cells. At the molecular level, tumor suppressor menin was found to be a target of miR-421. Furthermore, downregulation of menin by small interfering RNA oligos exhibited similar effects with overexpression of miR-421. On the other hand, overexpression of menin partially reversed the proliferative effects of miR-421 in neuroblastoma cells. Collectively, miR-421 may promote neuroblastoma cell growth and motility partially by targeting menin.
神经母细胞瘤是婴幼儿最常见的颅外实体瘤，其特点是自发缓解率高。大量报道表明，微小RNA（miRNA）在癌症进展中发挥着重要作用，包括细胞增殖、凋亡、侵袭、转移和血管生成。miR-421在某些恶性肿瘤中作为癌基因发挥作用。然而，其在神经母细胞瘤中的作用仍知之甚少。在本研究中，我们发现与配对的相邻正常组织相比，神经母细胞瘤组织中miR-421水平升高。miR-421的强制过表达显著增强了神经母细胞瘤细胞的增殖、细胞周期进程、迁移和侵袭。在分子水平上，发现肿瘤抑制因子Menin是miR-421的一个靶点。此外，小干扰RNA寡核苷酸下调Menin表现出与miR-421过表达类似的效果。另一方面，Menin的过表达部分逆转了miR-421对神经母细胞瘤细胞的增殖作用。总体而言，miR-421可能通过靶向Menin部分促进神经母细胞瘤细胞的生长和运动。
