Abba Martin C, Canzoneri Romina, Gurruchaga Agustina, Lee Jaeho, Tatineni Pradeep, Kil Hyunsuk, Lacunza Ezequiel, Aldaz C Marcelo
Centro de Investigaciones Inmunológicas Básicas y Aplicadas (CINIBA), Facultad de Ciencias Médicas, Universidad Nacional de La Plata, La Plata CP1900, Argentina.
Department of Epigenetics and Molecular Carcinogenesis, The University of Texas M.D. Anderson Cancer Center, Science Park, Smithville, TX 78957, USA.
Int J Mol Sci. 2020 Oct 8;21(19):7407. doi: 10.3390/ijms21197407.
Long intergenic non-protein coding RNA 885 () was identified as significantly upregulated in breast ductal carcinoma in situ (DCIS). The aim of this study was to characterize the phenotypic effects and signaling pathways modulated by in non-invasive and invasive breast cancer models. We determined that induces premalignant phenotypic changes by increasing cell proliferation, motility, migration and altering 3D growth in normal and DCIS breast cell lines. Transcriptomic studies (RNA-seq) identified the main signaling pathways modulated by which include bioprocesses related to TP53 signaling pathway and proliferative signatures such as activation of EREG, EGFR and FOXM1 pathways. silencing in breast cancer lines overexpressing this lncRNA leads to downregulation of proliferation related transcripts such as , , and to significant decrease in cell migration and motility. TCGA-BRCA data analyses show an association between high expression and worse overall survival in patients with primary invasive breast carcinomas ( 0.024), suggesting that the pro-tumorigenic effects of overexpression persist post-invasion. We conclude that behaves as a positive regulator of cell growth both in normal and DCIS breast cells possibly operating as a ceRNA and representing a novel oncogenic lncRNA associated with early stage breast cancer progression.
长链基因间非编码RNA 885()在乳腺导管原位癌(DCIS)中被鉴定为显著上调。本研究的目的是在非侵袭性和侵袭性乳腺癌模型中表征由其调节的表型效应和信号通路。我们确定在正常和DCIS乳腺细胞系中,通过增加细胞增殖、运动性、迁移并改变三维生长,诱导癌前表型变化。转录组学研究(RNA测序)确定了由其调节的主要信号通路,包括与TP53信号通路相关的生物过程以及增殖特征,如EREG、EGFR和FOXM1通路的激活。在过表达这种lncRNA的乳腺癌细胞系中沉默该基因会导致增殖相关转录本如、、的下调,并导致细胞迁移和运动性显著降低。TCGA-BRCA数据分析显示,原发性浸润性乳腺癌患者中高表达与较差的总生存期相关(0.024),这表明过表达的促肿瘤作用在侵袭后仍然存在。我们得出结论,在正常和DCIS乳腺细胞中均作为细胞生长的正调节因子发挥作用,可能作为一种竞争性内源RNA发挥作用,并代表一种与早期乳腺癌进展相关的新型致癌lncRNA。