Neurobiology Institute, Jining Medical University, Jining, P.R. China.
Int J Immunopathol Pharmacol. 2017 Sep;30(3):264-271. doi: 10.1177/0394632017720546. Epub 2017 Aug 1.
Our previous high-throughput sequencing indicated that rno-miR-1298 was down-regulated in ischemia-reperfusion model of rat. However, little is known about the function and molecular mechanism of rno-miR-1298 in rat tumor cell. In this study, rno-miR-1298 was detected to be significantly down-regulated in rat tumor C6 cells. Moreover, overexpression of rno-miR-1298 obviously inhibited the proliferation and induced apoptosis in C6 cells. SET domain containing 7 (SETD 7) was identified to be a target of rno-miR-1298 using bioinformatics and luciferase reporter assays. Overexpression of rno-miR-1298 markedly reduced the expression of SETD 7 at protein level. Knockdown of SETD 7 also suppressed proliferation and promoted apoptosis in C6 cells. It was indicated that rno-miR-1298 affected cell proliferation and apoptosis of rat tumor cells by targeting SETD 7. Thus, the newly identified miR-1298/SETD 7 expands the elaboration of the mechanisms of the development and progression of tumors and may provide therapeutic target for tumors of nervous system.
我们之前的高通量测序表明,rno-miR-1298 在大鼠缺血再灌注模型中表达下调。然而,关于 rno-miR-1298 在大鼠肿瘤细胞中的功能和分子机制知之甚少。在这项研究中,rno-miR-1298 在大鼠肿瘤 C6 细胞中明显下调。此外,rno-miR-1298 的过表达明显抑制了 C6 细胞的增殖并诱导了细胞凋亡。生物信息学和荧光素酶报告实验鉴定 SET 结构域包含 7 (SETD7)是 rno-miR-1298 的靶基因。rno-miR-1298 的过表达显著降低了 SETD7 的蛋白水平表达。SETD7 的敲低也抑制了 C6 细胞的增殖并促进了细胞凋亡。这表明 rno-miR-1298 通过靶向 SETD7 影响大鼠肿瘤细胞的增殖和细胞凋亡。因此,新鉴定的 miR-1298/SETD7 扩展了肿瘤发生和发展机制的阐述,并可为神经系统肿瘤提供治疗靶点。