LINC885: AN ONCOGENIC LONG NON-CODING RNA ASSOCIATED TO EARLY PROGRESSION OF BREAST CANCER.

LACUNZA E; CANZONERI R; GURRUCHAGA A; PALMA S; LEE J; ALDAZ CM; ABBA MC

Simposio; SISTAM 2018 IUBMB Focused Meeting The Fourth South American Symposium in Signal Transduction and Molecular Medicine; 2018

Long non-coding RNAs (lncRNA) are a type of non-coding RNAs (ncRNAs) that exceed 200 nucleotides in length. They are relatively abundant components of the mammalian transcriptome and have been implicated in several cellular functions, normal development, organogenesis and human disease. Numerous lncRNAs have been associated to breast cancer progression. In a previous study, we identified a group of novel lncRNAs differentially expressed between normal and ductal carcinoma in situ (DCIS). Among those lncRNAs the LINC885 was found to display prognostic value independent of ER/PR receptor status, tumoral grade and lymph node status, when evaluated in data of patients with invasive ductal carcinoma (IDC). The aim of this study was to characterize the in vitro and in vivo effects of LINC885 in non-invasive and invasive cellular models as a novel breast cancer progression driver lncRNA. We characterized the phenotypic effects of overexpressing LINC885 in normal and DCIS cell lines (MCF10 and DCIS.COM); on the other side, we evaluated the effects of silencing the target lncRNAs in an invasive breast cancer cell line (MCF7). Furthermore, transcriptomic (RNA-Seq) and proteomic (RNA-pull down, TAP-MS) analysis were conducted to identify signaling pathways modulated by LINC885 in stably transfected cells. The results showed that expression variations of LINC885 affected processes such as colony formation, cell proliferation and migration. Functional enrichment analysis of deregulated transcripts on LINC885 stable transfected cells revealed specific bioprocess related to TP53, EGFR and FOXM1 signaling pathways associated to a proliferative signature. In addition, analysis of BRCA-TCGA data showed an association between high LINC885 expression and decreased overall survival (p=0.02) in primary invasive breast carcinomas patients. Based on these studies, we conclude that LINC885 represent a novel oncogenic lncRNA associated to early stage breast cancer progression.