Pan Jun, Lu Fengfei, Xu Hongchao, Wang Qifu, Lin Chunnan, Zhang Shizhong
The National Key Clinic Specialty, The Neurosurgery Institute of Guangdong Province, Guangdong, 510282, China.
Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Guangdong, 510282, China.
Tumour Biol. 2016 Jul;37(7):9663-70. doi: 10.1007/s13277-016-4788-5. Epub 2016 Jan 22.
MicroRNAs (miRNAs), a kind of endogenous non-coding RNAs, regulate gene expression through binding to the 3'-untranslational region (UTR) of target messenger RNAs (mRNAs) and act as endogenous agents of RNA interference, resulting in either mRNA degradation or translational repression. MiR-31 has been demonstrated to be associated with the development and progression of glioma. However, the underlying molecular mechanism remains largely unclear. In the present study, we demonstrated that miR-31 only inhibited the cell migration and invasion, as well as the expression of a known miR-31 target oncogene radixin, in U251 glioma cells that expressed low level of p21; however, miR-31 showed no above effects on glioma SHG44 cells that highly expressed p21. Moreover, upregulation of p21 in U251 cells reversed the suppressive effects of miR-31 on the cell migration and invasion, suggesting that low p21 level is necessary for the miR-31-mediated inhibitory effects on glioma. Furthermore, analysis for 35 glioma specimens showed that the expression of radixin was negatively correlated with the miR-31 level in glioma tissues with low p21 expression; however, no such correlation was found in glioma tissues with high p21 level, further supporting that the low p21 level is necessary for the suppressive effect of miR-31 on the expression of its target oncogenes. In summary, our study demonstrates that the suppressive effect of miR-31 on glioma cell migration and invasion is p21-dependent, and suggests that miR-31 may be used for the treatment of patients with p21-deficent glioma.
微小RNA(miRNA)是一类内源性非编码RNA,通过与靶信使核糖核酸(mRNA)的3'非翻译区(UTR)结合来调节基因表达,并作为RNA干扰的内源性介质,导致mRNA降解或翻译抑制。已证明miR-31与胶质瘤的发生和发展有关。然而,其潜在的分子机制仍不清楚。在本研究中,我们证明miR-31仅在p21表达水平低的U251胶质瘤细胞中抑制细胞迁移和侵袭以及已知的miR-31靶癌基因根蛋白的表达;然而,miR-31对高表达p21的胶质瘤SHG44细胞没有上述作用。此外,U251细胞中p21的上调逆转了miR-31对细胞迁移和侵袭的抑制作用,表明低p21水平是miR-31介导的对胶质瘤抑制作用所必需的。此外,对35个胶质瘤标本的分析表明,在p21表达低的胶质瘤组织中,根蛋白的表达与miR-31水平呈负相关;然而,在p21水平高的胶质瘤组织中未发现这种相关性,进一步支持低p21水平是miR-31对其靶癌基因表达抑制作用所必需的。总之,我们的研究表明miR-31对胶质瘤细胞迁移和侵袭的抑制作用是p21依赖性的,并表明miR-31可用于治疗p21缺乏的胶质瘤患者。