Role of LIN28, a RNA-binding protein, in adrenocortical tumorigenesis

Abstract

Adrenocortical Carcinoma is a rare and frequently aggressive endocrine tumor. Currently, there are limited data to define histological or molecular markers that can reliably distinguish benign tumors from those with unfavorable clinical outcome, mainly in the pediatric population. LIN28, a highly conserved RNA-binding protein, has emerged as an important regulator of let-7, a microRNA widely known for its tumor suppressor actions. LIN28 also has a key role in cellular reprogramming and pluripotency induction. Recently, LIN28 has shown to promote malignant transformation and to be activated in a variety of human tumors with an overall frequency of around 15%, specifically in the subset that is poorly differentiated and carries the worst prognosis. The aims of this study are to: 1) ascertain the expression of LIN28 in pediatric and adult adrenocortical tumors and correlate with clinical, laboratory and prognostic data of these patients; 2) evaluate chromosomal gains or losses in the LIN28 locus; 3) evaluate the effects of LIN28 gene silencing on adrenocortical tumor cell line proliferation; 4) compare gene expression profile of adrenocortical tumor cell lines before and after LIN28 gene silencing. (AU)