Abstract 5208: MiR-22 is frequently down-regulated in medulloblastomas, and inhibits cell proliferation via the novel target PAPST1

Abstract

Abstract Medulloblastoma (WHO grade IV) is the most frequent malignant CNS tumor in children. MicroRNAs (miRNAs, miRs) are small non-coding RNAs that target protein-coding mRNAs that play roles in a variety of cellular processes through regulating multiple target genes. In the present study, we analyzed miR-22 expression and its effect on cell proliferation and apoptosis in medulloblastomas. Quantitative RT-PCR revealed significantly lower expression of miR-22 in 19/25 (76%) medulloblastomas, D341, DAOY and ONS-76 medulloblastoma cells and primary cultured medulloblastomas cells, compared to normal cerebellum. Forced expression of miR-22 by lentiviral vector transfection reduced cell proliferation and induced apoptosis in DAOY and ONS-76 cells. DAOY cells with miR-22 overexpression in nude mice yielded tumors smaller than those originated from control DAOY cells. Microarray analysis in DAOY cells with forced miR-22 expression showed significant changes in expression profiles; PAPST1 being the most significantly (10-fold) down-regulated gene. Quantitative RT-PCR revealed PAPST1 up-regulation in 18/25 (72%) medulloblastomas. Furthermore, the results of luciferase reporter assay in ONS-76 cells suggested that miR-22 directly targets the PAPST1 gene. Thus, frequently down-regulated miR-22 expression is associated with cell proliferation in medulloblastomas, at least in part via PAPST1, which is a novel target of miR-22. Citation Format: Qing-Fu Xu, Jesse Chung-sean Pang, Hui Yang, Sheng-Qing Lv, Hiroko Ohgaki. MiR-22 is frequently down-regulated in medulloblastomas, and inhibits cell proliferation via the novel target PAPST1. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5208. doi:10.1158/1538-7445.AM2014-5208