Laboratory of Human Retrovirology and Immunoinformatics, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, 21702, USA.
AIDS Monitoring Laboratory, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, 21702, USA.
Sci Rep. 2018 Jan 17;8(1):900. doi: 10.1038/s41598-018-19259-4.
We have previously demonstrated that Interleukin-27 differentially regulates the expression of seven novel microRNAs. Here we elucidate the functional significance of these novel microRNAs. Of the seven microRNAs, over expression of miRNA-6852 (miR-SX4) mimic induces cell cycle arrest at G2/M phase and induces necrosis in HEK293 and panel of cervical cancer cells (Human Papilloma Virus (HPV) infected cell lines; HeLa, CaSki and SiHa cells). To define the mechanism of the miR-SX4-mediated G2/M arrest, a microarray gene chip array and western blot analysis were performed. FoxM1, a transcription factor is identified as a key protein down-regulated by miR-SX4, even though the miR-SX4 does not target 3'UTR of FoxM1. Knock down of FoxM1 using si-RNA demonstrate that FoxM1 silenced cell induces G2/M cell cycle arrest and necrosis. Our data demonstrated for the first time that miR-SX4 could be a potent anti-cancer microRNA.
我们之前已经证明白细胞介素-27 可以差异调节七种新的 microRNA 的表达。在这里，我们阐明了这些新的 microRNA 的功能意义。在这七种 microRNA 中，miR-SX4（miRNA-6852）模拟物的过表达导致 HEK293 和一组宫颈癌细胞（人乳头瘤病毒（HPV）感染细胞系；HeLa、CaSki 和 SiHa 细胞）在 G2/M 期停滞并诱导坏死。为了定义 miR-SX4 介导的 G2/M 期阻滞的机制，进行了微阵列基因芯片和 Western blot 分析。FoxM1，一种转录因子，被确定为 miR-SX4 下调的关键蛋白，尽管 miR-SX4 并不靶向 FoxM1 的 3'UTR。使用 si-RNA 敲低 FoxM1 证明 FoxM1 沉默的细胞诱导 G2/M 细胞周期停滞和坏死。我们的数据首次表明，miR-SX4 可能是一种有效的抗癌 microRNA。
