Zhang Daobao, Liu Zhiyong, Zheng Niandong, Wu Honggang, Zhang Zhao, Xu Jianguo
Neurosurgery of West China Hospital, Sichuan University, Chengdu 610000, PR China.
Neurosurgery of the People's Hospital of Leshan, Leshan 614000, PR China.
Saudi J Biol Sci. 2018 Jul;25(5):947-952. doi: 10.1016/j.sjbs.2018.02.015. Epub 2018 Mar 8.
Malignant glioma is the most common and lethal type of primary tumor of the central nervous system. The incidence of glioma is increasing year by year. In recent years, a variety of new treatment methods have emerged, among which gene therapy has become a hotspot. MicroRNAs (miRNAs) are a class of small non-coding single-strand RNAs that negatively regulate gene expression at the post-transcriptional and/or translational level by binding loosely complimentary sequences in the 3' untranslated regions (UTRs) of target mRNAs. Several miRNAs have been reported to modulate glioma progression. This study aimed to determine the function of miR-30b-5p in glioma and its underlying molecular mechanism. miR-30b-5p expression was significantly lower in gliomas than the normal brain tissues. Overexpression of miR-30b-5p was found to significantly inhibit glioma cell proliferation in vitro. Further, MTDH expression was significantly higher in the gliomas compared with the normal brain tissues. In addition, MTDH was validated as direct target of miR-30b-5p. Moreover, cellular proliferation was increased after MTDH overexpression in the glioma cells, which reversed the effects of miR-30b-5p. Taken together, these results reveal miR-30b-5p impacts glioma cell proliferation via direct targeting MTDH and could be a potential novel therapeutic target for the treatment of glioma.
恶性胶质瘤是中枢神经系统最常见且致命的原发性肿瘤类型。胶质瘤的发病率逐年上升。近年来，出现了多种新的治疗方法，其中基因治疗已成为一个热点。微小RNA（miRNA）是一类小的非编码单链RNA，通过与靶mRNA的3'非翻译区（UTR）中松散互补的序列结合，在转录后和/或翻译水平对基因表达进行负调控。据报道，几种miRNA可调节胶质瘤进展。本研究旨在确定miR-30b-5p在胶质瘤中的功能及其潜在的分子机制。与正常脑组织相比，miR-30b-5p在胶质瘤中的表达显著降低。发现miR-30b-5p过表达可在体外显著抑制胶质瘤细胞增殖。此外，与正常脑组织相比，MTDH在胶质瘤中的表达显著更高。另外，MTDH被证实为miR-30b-5p的直接靶点。而且，在胶质瘤细胞中过表达MTDH后细胞增殖增加，这逆转了miR-30b-5p的作用。综上所述，这些结果表明miR-30b-5p通过直接靶向MTDH影响胶质瘤细胞增殖，可能是治疗胶质瘤的一个潜在新治疗靶点。
