Pang Fei, Zha Ruopeng, Zhao Yingjun, Wang Qifeng, Chen Di, Zhang Zhenfeng, Chen Taoyang, Yao Ming, Gu Jianren, He Xianghuo
Shanghai Medical College, Fudan University, Shanghai, China; State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
PLoS One. 2014 Mar 5;9(3):e90867. doi: 10.1371/journal.pone.0090867. eCollection 2014.
Liver cancer is one of leading causes of cancer-related deaths. A deeper mechanistic understanding of liver cancer could lead to the development of more effective therapeutic strategies. In our previous work, we screened 646 miRNAs and identified 11 that regulate liver cancer cell migration. The current study shows that miR-525-3p is frequently up-regulated in liver cancer tissues, and enhanced expression of miR-525-3p can promote liver cancer cell migration and invasion. Zinc finger protein 395 (ZNF395) is the direct functional target gene for miR-525-3p, and it is frequently down-regulated in liver cancer tissues. High expression of ZNF395 can significantly inhibit while knockdown of ZNF395 expression can markedly enhance the migration and invasion of liver cancer cells, suggesting that ZNF395 suppresses metastasis in liver cancer. Down-regulation of ZNF395 can mediate miR-525-3p induced liver cancer cell migration and invasion. In conclusion, miR-525-3p promotes liver cancer cell migration and invasion by directly targeting ZNF395, and the fact that miR-525-3p and ZNF395 both play important roles in liver cancer progression makes them potential therapeutic targets.
肝癌是癌症相关死亡的主要原因之一。对肝癌进行更深入的机制研究有助于开发更有效的治疗策略。在我们之前的研究中,我们筛选了646种微小RNA(miRNA),并鉴定出11种可调节肝癌细胞迁移的miRNA。目前的研究表明,miR-525-3p在肝癌组织中经常上调,其表达增强可促进肝癌细胞的迁移和侵袭。锌指蛋白395(ZNF395)是miR-525-3p的直接功能靶基因,在肝癌组织中经常下调。ZNF395的高表达可显著抑制肝癌细胞的迁移和侵袭,而敲低ZNF395的表达则可显著增强肝癌细胞的迁移和侵袭,这表明ZNF395抑制肝癌转移。ZNF395的下调可介导miR-525-3p诱导的肝癌细胞迁移和侵袭。总之,miR-525-3p通过直接靶向ZNF395促进肝癌细胞的迁移和侵袭,并且miR-525-3p和ZNF395在肝癌进展中均起重要作用,这使其成为潜在的治疗靶点。