Indirect Down-regulation of Tumor-suppressive let-7 Family MicroRNAs by LMO1 in Neuroblastoma

Abstract

Background/aim: Overall survival for the high-risk group of neuroblastoma (NB) patients still remains at 40-50%, necessitating the establishment of a curable treatment. LIM domain only 1 (LMO1) gene encoding a transcriptional regulator is an NB-susceptibility gene with a tumor-promoting activity. Previously we conducted chromatin immunoprecipitation and DNA sequencing analyses on NB cell lines and identified 3 protein-coding genes regulated by LMO1. In this study, we extended our analyses to capture microRNA genes directly or indirectly regulated by LMO1.

Materials and methods: Using microarrays, we conducted a comparative gene expression analysis on an NB cell line SK-N-SH; between the cells with and without LMO1 suppression.

Results: Overall, 18 microRNAs were identified to be indirectly down-regulated by LMO1 including 7 microRNAs of the let-7 family, whose cell proliferation inhibitory activity was observed.

Conclusion: Target genes of the LMO1-regulated microRNAs and their relevant pathways may be a potential therapeutic target.

Keywords: LMO1; Neuroblastoma; let-7; microRNA; pediatric cancer.