Wang Zheng-Shi, Zhong Ming, Bian Yu-Hai, Mu Yi-Fei, Qin Shao-Lan, Yu Min-Hao, Qin Jun
Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, P.R. China.
Oncotarget. 2016 Jul 12;7(28):44266-44276. doi: 10.18632/oncotarget.10023.
Aberrantly expressed microRNAs contribute to the initiation and progression of human cancers. However, the underlying functions of microRNA-187 (miR-187) in colorectal cancer (CRC) remain largely unexplored. Here, we demonstrated that miR-187 was significantly down-regulated in CRC tissues and cell lines compared to their normal counterparts. By Kaplan-Meier analysis, we revealed that decreased miR-187 expression was closely associated with shorter overall survival and relapse-free survival of patients with CRC. By gain- and loss-of-function studies, we showed that miR-187 remarkably suppressed CRC cell proliferation, migration, invasion, and promoted cell apoptosis. Furthermore, bioinformatics analysis and luciferase reporter assay identified that CD276 was the direct functional target of miR-187 in CRC. Genetic silencing of CD276 recapitulated similar phenotype as observed in over-expression of miR-187, and restoration of CD276 completely rescued the inhibitory effect of miR-187 in CRC cells. Taken together, our study implied the essential roles of miR-187 in suppressing CRC progression, and a novel link between miR-187 and CD276 in CRC.
异常表达的微小RNA促进人类癌症的发生和发展。然而，微小RNA - 187（miR - 187）在结直肠癌（CRC）中的潜在功能仍 largely未被探索。在此，我们证明与正常组织和细胞系相比，miR - 187在CRC组织和细胞系中显著下调。通过Kaplan - Meier分析，我们发现miR - 187表达降低与CRC患者较短的总生存期和无复发生存期密切相关。通过功能获得和功能缺失研究，我们表明miR - 187显著抑制CRC细胞增殖、迁移、侵袭并促进细胞凋亡。此外，生物信息学分析和荧光素酶报告基因检测确定CD276是miR - 187在CRC中的直接功能靶点。CD276的基因沉默重现了与miR - 187过表达相似的表型，而CD276的恢复完全挽救了miR - 187对CRC细胞的抑制作用。综上所述，我们的研究表明miR - 187在抑制CRC进展中起重要作用，并且在CRC中miR - 187与CD276之间存在新的联系。
