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