title: MicroRNA-21 Down-regulates Rb1 Expression by Targeting PDCD4 in Retinoblastoma.
abstract: Retinoblastoma (RB) is a children's ocular cancer caused by mutated retinoblastoma 1 (Rb1) gene on both alleles. Rb1 and other related genes could be regulated by microRNAs (miRNA) via complementarily pairing with their target sites. MicroRNA-21 (miR-21) possesses the oncogenic potential to target several tumor suppressor genes, including PDCD4, and regulates tumor progression and metastasis. However, the mechanism of how miR-21 regulates PDCD4 is poorly understood in RB. We investigated the expression of miRNAs in RB cell lines and identified that miR-21 is one of the most deregulated miRNAs in RB. Using qRT-PCR, we verified the expression level of several miRNAs identified by independent microarray assays, and analyzed miRNA expression patterns in three RB cell lines, including Weri-Rb1, Y79 and RB355. We found that miR-19b, -21, -26a, -195 and -222 were highly expressed in all three cell lines, suggesting their potential role in RB tumorigenesis. Using the TargetScan program, we identified a list of potential target genes of these miRNAs, of which PDCD4 is one the targets of miR-21. In this study, we focused on the regulatory mechanism of miR-21 on PDCD4 in RB. We demonstrated an inverse correlation between miR-21 and PDCD4 expression in Weri-Rb1 and Y79 cells. These data suggest that miR-21 down-regulates Rb1 by targeting PDCD4 tumor suppressor. Therefore, miR-21 could serve as a therapeutic target for retinoblastoma.
authors.affiliation: 1. Department of Ophthalmology, Xi'an Jiaotong University First Affiliated Hospital, Xi'an, China.
authors.forename: Fengmei
authors.initials: F
authors.lastname: Shen
authors.affiliation: 2. Department of Medicine, Division of Genomic Medicine, and Department of Microbiology, Immunology and Tropical Medicine, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
authors.forename: Meng-Hsuan
authors.initials: MH
authors.lastname: Mo
authors.affiliation: 2. Department of Medicine, Division of Genomic Medicine, and Department of Microbiology, Immunology and Tropical Medicine, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
authors.forename: Liang
authors.initials: L
authors.lastname: Chen
authors.affiliation: 2. Department of Medicine, Division of Genomic Medicine, and Department of Microbiology, Immunology and Tropical Medicine, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
authors.forename: Shejuan
authors.initials: S
authors.lastname: An
authors.affiliation: 2. Department of Medicine, Division of Genomic Medicine, and Department of Microbiology, Immunology and Tropical Medicine, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Tan
authors.affiliation: 2. Department of Medicine, Division of Genomic Medicine, and Department of Microbiology, Immunology and Tropical Medicine, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
authors.forename: Yebo
authors.initials: Y
authors.lastname: Fu
authors.affiliation: 3. Department of Pathology, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
authors.forename: Katayoon
authors.initials: K
authors.lastname: Rezaei
authors.affiliation: 4. Department of Surgery, Xi'an Jiaotong University First Affiliated Hospital, Xi'an, China.
authors.forename: Zuoren
authors.initials: Z
authors.lastname: Wang
authors.affiliation: 1. Department of Ophthalmology, Xi'an Jiaotong University First Affiliated Hospital, Xi'an, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: 2. Department of Medicine, Division of Genomic Medicine, and Department of Microbiology, Immunology and Tropical Medicine, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
authors.forename: Sidney W
authors.initials: SW
authors.lastname: Fu
keywords: PDCD4.; Retinoblastoma; miR-21; miRNA