Somatic Copy-Number Alterations across Human Cancers from LncRNA Perspective

Abstract

The genome of a tumor cell presents thousands of genomic alterations including base-substitutions and somatic copy number alterations (SCNAs). SCNAs comprise amplifications and deletions of big chromosomal regions usually containing hundreds of genes. Some of these regions harbor well-studied cancer drivers; however many others do not contain a known driver. The analysis of SCNA focusing on the non-coding genome helped us pinpoint a list of copy number altered long noncoding RNAs (lncRNAs). In order to validate our findings we experimentally characterized functionally and mechanistically a lncRNA amplified in lung cancer which we named LUAD-amp-1. LUAD-amp-1 acts as an oncogenic lncRNA, and its expression is induced by the transcription factor NF-B upon TNF treatment. Moreover, LUAD-amp-1 is implicated in the inhibition of a set of NF-B regulated genes including TNF itself. LUAD-amp-1 molecular mechanism relies on its association with SART3, altering its localization and modulating the nuclear translocation of its associated protein USP4.