Wang Ren, Zuo Xiaohua, Wang Kai, Han Qiu, Zuo Jiandong, Ni Hongzao, Liu Wenguang, Bao Hongguang, Tu Yiming, Xie Peng
Department of Pediatric Surgery, Huai'an Women and Children's Hospital Huai'an 223002, Jiangsu, PR China.
Department of Pain Management, Huai'an Hospital Affiliated to Xuzhou Medical University, Second People's Hospital of Huai'an Huai'an, Jiangsu, PR China.
Am J Cancer Res. 2018 Dec 1;8(12):2507-2517. eCollection 2018.
MicroRNA-485-5p (miR-485-5p) has been reported to be involved in the development and progression of human cancers; however, its role in glioma remains unclear. In the present study, we found that miR-485-5p was significantly down-regulated in both glioma tissues and cell lines. Functional experiments indicated that enhanced expression of miR-485-5p attenuated glioma cell proliferation in vitro and in vivo, and induced glioma cells cycle arrest in G1. MiR-485-5p was found to directly bind to the 3'-UTR of paired box 3 (PAX3) and decrease its expression of protein level, which further inhibits the proliferation of glioma. The decreasing of PAX3 was found to lead to the accumulation of p-JNK. Mechanistic studies revealed that restoring the expression of PAX3 alleviated miR-485-5p-induced inhibition of proliferation of glioma cells. Taken together, these findings suggest that PAX3 modulation by miR-485-5p has an important role in regulating glioma proliferation, and miR-485-5p might be a novel therapeutic target for glioma.
据报道,微小RNA-485-5p(miR-485-5p)参与人类癌症的发生和发展;然而,其在胶质瘤中的作用仍不清楚。在本研究中,我们发现miR-485-5p在胶质瘤组织和细胞系中均显著下调。功能实验表明,miR-485-5p表达增强可在体外和体内减弱胶质瘤细胞增殖,并诱导胶质瘤细胞在G1期发生细胞周期阻滞。发现miR-485-5p直接结合配对盒3(PAX3)的3'-非翻译区并降低其蛋白水平表达,进而抑制胶质瘤增殖。发现PAX3减少会导致p-JNK积累。机制研究表明,恢复PAX3表达可减轻miR-485-5p诱导的胶质瘤细胞增殖抑制。综上所述,这些发现表明miR-485-5p对PAX3的调控在调节胶质瘤增殖中起重要作用,miR-485-5p可能是胶质瘤的一个新的治疗靶点。