Fabre María Laura, Canzoneri Romina, Gurruchaga Agustina, Lee Jaeho, Tatineni Pradeep, Kil Hyunsuk, Lacunza Ezequiel, Aldaz C Marcelo, Abba Martín Carlos
Centro de Investigaciones Inmunológicas Básicas y Aplicadas (CINIBA), Facultad de Ciencias Médicas, Universidad Nacional de La Plata, La Plata 1900, Argentina.
Department of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
Cancers (Basel). 2022 Jun 7;14(12):2819. doi: 10.3390/cancers14122819.
Long non-coding RNAs are increasingly being recognized as cancer biomarkers in various malignancies, acting as either tumor suppressors or oncogenes. The long non-coding intergenic RNA was identified as significantly upregulated in breast ductal carcinoma in situ. The aim of this study was to characterize expression, localization, and phenotypic and molecular effects in non-invasive and invasive breast cancer cells. We determined that is an estrogen-estrogen receptor-modulated lncRNA enriched in the cytoplasmic fraction of luminal A/B breast cancer cells that is associated with worse overall survival in patients with primary invasive breast carcinomas. Transcriptomic studies in normal and DCIS cells identified the main signaling pathways modulated by , which mainly involve bioprocesses related to innate and adaptive immune responses, extracellular matrix remodeling, cell adhesion, and activation of AP-1 signaling pathway. We determined that induces premalignant phenotypic changes by increasing cell migration in normal breast cells. Moreover, high expression in invasive carcinomas was associated with a pro-tumorigenic immune environment and a favorable predicted response to immunotherapy both in luminal and basal-like subtypes compared with low--expression tumors. We conclude that behaves as an oncogenic and immune-related lncRNA involved with early-stage breast cancer progression.
长链非编码RNA越来越被认为是各种恶性肿瘤中的癌症生物标志物,可作为肿瘤抑制因子或癌基因发挥作用。长链非编码基因间RNA被确定在乳腺导管原位癌中显著上调。本研究的目的是描述其在非侵袭性和侵袭性乳腺癌细胞中的表达、定位以及表型和分子效应。我们确定,它是一种雌激素-雌激素受体调节的长链非编码RNA,富集于腔A/B型乳腺癌细胞的细胞质部分,与原发性浸润性乳腺癌患者较差的总生存期相关。对正常细胞和导管原位癌(DCIS)细胞的转录组学研究确定了由其调节的主要信号通路,这些通路主要涉及与先天性和适应性免疫反应、细胞外基质重塑、细胞黏附以及AP-1信号通路激活相关的生物过程。我们确定,它通过增加正常乳腺细胞的迁移诱导癌前表型变化。此外,与低表达肿瘤相比,浸润性癌中高表达与促肿瘤免疫环境以及管腔型和基底样亚型对免疫治疗的良好预测反应相关。我们得出结论,它作为一种致癌和免疫相关的长链非编码RNA参与早期乳腺癌进展。