Shen Lei, Chen Xiao-Dong, Zhang Yao-Hui
Department of Orthopaedic Surgery, Xinhua Hospital, Shanghai JiaoTong University School of Medicine, No.1665 kongjiang Rd., Shanghai, 200092, People's Republic of China.
Tumour Biol. 2014 Mar;35(3):2069-74. doi: 10.1007/s13277-013-1274-1. Epub 2013 Oct 15.
MicroRNAs are a class of small noncoding RNAs that function as critical gene regulators through targeting mRNAs for translational repression or degradation. Several studies have indicated that abnormal expression of miRNAs occurs frequently in human osteosarcoma. In the present study, we found that miR-128 expression was significantly increased in osteosarcoma tissues compared to adjacent normal tissues. Ectopic overexpression of miR-128 significantly promoted while suppression of miR-128 by its antisense inhibited the proliferation of MG63 and U2OS cells. At the molecular level, our results demonstrated that miR-128 overexpression could repress expression of PTEN by directly targeting PTEN 3'-untranslated region. Consistently, downstream AKT signaling was altered by miR-128 overexpression or knockdown. Therefore, our results suggest that miR-128 plays an important role in the proliferation of human osteosarcoma cells by directly regulation of PTEN/AKT signaling.
微小RNA是一类小的非编码RNA,通过靶向mRNA进行翻译抑制或降解来发挥关键的基因调节作用。多项研究表明,微小RNA的异常表达在人类骨肉瘤中频繁发生。在本研究中,我们发现与相邻正常组织相比,骨肉瘤组织中miR-128的表达显著增加。miR-128的异位过表达显著促进了MG63和U2OS细胞的增殖,而其反义寡核苷酸抑制miR-128则抑制了这些细胞的增殖。在分子水平上,我们的结果表明,miR-128过表达可通过直接靶向PTEN的3'-非翻译区来抑制PTEN的表达。同样,miR-128过表达或敲低会改变下游AKT信号通路。因此,我们结果表明,miR-128通过直接调节PTEN/AKT信号通路在人类骨肉瘤细胞增殖中发挥重要作用。