LONG INTERGENIC NON-CODING RNA 885 IS INVOLVED IN NON-INVASIVE AND INVASIVE STAGES OF BREAST CANCER PROGRESSION

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

Congreso; REUNIÓN CONJUNTA DE SOCIEDADES DE BIOCIENCIAS; 2017

Long non-coding RNAs (lncRNAs) are defined as RNA transcripts longer than 200 nt which do not encode proteins.Although our understanding is limited, lncRNAs have been shownto be important players in normal development, organogenesis,multiple cellular processes and human disease. Multiple lncRNAshave been reported associated with breast cancer progression. Ina recent study, RNA-Seq analysis allowed us to identify a groupof novel lncRNAs as differentially expressed between normaland ductal carcinoma in situ (DCIS). The aim of this study was tocharacterize the in vitro and in vivo effects of LINC885 in non-invasiveand invasive models as a novel breast cancer progression driverlncRNA. First, we performed a phenotypic characterization of theeffects of overexpressing LINC885 in a prototypic normal and DCIScell lines (MCF10 and DCIS.COM) and vice-versa; we analyzed theeffects of silencing the target lncRNAs in invasive breast cancerlines displaying their overexpression. Second, transcriptomic (RNASeq)and RNA-pull down (TAP-MS) analyses were also applied toidentify the signaling pathway modulated by LINC885 among stabletransfected breast cell lines. LINC885 stable overexpression ortransient silencing affected colony formation, cell proliferation andmigration. Functional enrichment analysis of deregulated transcriptsbetween LINC885 stable transfected cells vs. control cells revealedspecific bioprocess related to TP53 signaling pathway and alsoderegulated expression of genes associated with a proliferativesignature (EGFR and FOXM1 pathways). In addition, analysisof TCGA data showed an association between high LINC885expression and decreased overall survival (p=0.02) in patients withprimary invasive breast carcinomas. Based on these studies, weconclude that LINC885 overexpression represent a novel oncogeniclncRNA associated with early stage breast cancer progression.