Up-regulated miR-155 is associated with poor prognosis in childhood acute lymphoblastic leukemia and promotes cell proliferation targeting ZNF238

Abstract

ABSTRACT Objectives Acute lymphoblastic leukemia (ALL) is one of the most common malignancies in children. Our aim was to identify a novel miRNA that can predict prognosis of childhood ALL patients and explore its potential mechanism. Methods The miRNA expression profiles of childhood ALL were analyzed using GEO database and HiSeq instruments. The expression of miR-155 was examined by RT–PCR in 42 ALL patients. To investigate the role of miR-155 in ALL, four ALL cell lines (CEM-C1, Jurkat, MOLT-3 and MOLT-4) were transfected with miR-155 mimics, miR-155 inhibitors or corresponding controls. Dual-luciferase reporter system was applied to confirm the miR-155 target ZNF238. Moreover, proliferation and apoptosis were evaluated by MTT and flow cytometry. Results Dataset GSE56489 and GSE23024 demonstrated that miR-155 was up-regulated and ZNF238 was down-regulated at diagnosis status of ALL. High miR-155 expression was associated with poor outcome. Overexpressed miR-155 promoted ALL cell proliferation and inhibited apoptosis. Dual-luciferase reporter result showed that miR-155 directly regulated ZNF238. Silencing ZNF238 promoted cell proliferation in ALL cells. Discussion Our research indicating that miR-155 might possess potential value as a biomarker for predicting the prognosis of individuals. However, the role of ZNF238 in childhood ALL remain unknown. In the present study, we found the possible role of ZNF238 as a new tumor suppressor in ALL, which might be necessary for the antiproliferative functions of normal cells to counteract ALL formation. Conclusion Our results propose that miR-155 is in association with poor prognosis of childhood ALL. Furthermore, miR-155 could promote cell proliferation targeting ZNF238.