EXPRESSION OF miR-34 FAMILY OF microRNA AND CLINICAL OUTSOME OF NEUROBLASTOMA

Abstract

Neuroblastoma is one of the most common cancers in children that arises from sympathetic nervous system tissue with a high rate of incidence in Ukraine. Genetic abnormalities containing loss of chromosome 1p36 and 11q, MYCN amplification are strongly associated with poor prognosis of this disease. Despite rare TP53 mutations, p53 pathway is often inactivated in neuroblastoma, mostly by MDM2 overexpression. Members of miR-34 microRNA family are the most prevalent p53-induced miRNAs and important mediators of tumor suppression. MiR-34 microRNA family consists of three members: miR-34a is encoded by its own transcript from 1p36, whereas miR-34b and miR-34c share a common primary transcript in 11q. It is suggested that miR-34a is a suppressor of neuroblastoma tumor genesis, as it targets many oncogenes such as E2F3, BCL-2 and MYCN. In this study, we present evidence of miR-34 deregulation in neuroblastoma. A decrease of miR-34 expression was associated with unfavorable clinical and biological features of the disease. Low miR-34a expression was associated with a decrease of survival rates in groups of patients with MDM2 overexpression and MYCN not-amplified low expressed MDM2 neuroblastoma. Taking this into account, analysis of mir-34a expression can help to improve personalized therapy strategy and serve as additional marker for the stratification optimization in patients with neuroblastoma.