MicroRNA-203 Induces Apoptosis by TargetingBmi-1in YD-38 Oral Cancer Cells

Autor: Jong-Kyu Kim, Jin-Soo Kim, Sung-Min Moon, Choi Dw, Hong Sung Chun, Dong Kie Kim, Chun-Sung Kim, Dae-San Go, Hong-Beum Kim, Jin Kyeoung Kim, Sun Kyoung Yu, Su Gwan Kim, Seul-Ah Lee
Rok vydání: 2018
Předmět:
Zdroj: Anticancer Research. 38:3477-3485
ISSN: 1791-7530
0250-7005
Popis: Background/aim MicroRNAs (miRNAs) are closely associated with a number of cellular processes, including cell development, differentiation, proliferation, carcinogenesis, and apoptosis. The aim of the present study was to elucidate the molecular mechanisms underlying the tumor suppressor activity of miRNA-203 (miR-203) in YD-38 human oral cancer cells. Materials and methods Polymerase chain reaction analysis, MTT assay, DNA fragmentation assay, fluorescence-activated cell-sorting analysis, gene array, immunoblotting, and luciferase assay were carried out in YD-38 cells. Results miR-203 expression was significantly down-regulated in YD-38 cells compared to expression levels in normal human oral keratinocytes. miR-203 decreased the viability of YD-38 cells in a time- and dose-dependent manner. In addition, over-expression of miR-203 significantly increased not only DNA segmentation, but also the apoptotic population of YD-38 cells. These results indicate that miR-203 overexpression induces apoptosis in YD-38 cells. Target gene array analysis revealed that the expression of the polycomb complex protein gene Bmi-1, a representative oncogene, was significantly down-regulated by miR-203 in YD-38 cells. Moreover, both mRNA and protein levels of Bmi-1 were significantly reduced in YD-38 cells transfected with miR-203. These results indicate that Bmi-1 is a target gene of miR-203. A luciferase reporter assay confirmed that miR-203 suppressed Bmi-1 expression by directly targeting the 3'-untranslated region. Conclusion miR-203 induces apoptosis in YD-38 cells by directly targeting Bmi-1, which suggests its possible application as an anti-cancer therapeutic.
Databáze: OpenAIRE