Shen Yi, Katsaros Dionyssios, Loo Lenora W M, Hernandez Brenda Y, Chong Clayton, Canuto Emilie Marion, Biglia Nicoletta, Lu Lingeng, Risch Harvey, Chu Wen-Ming, Yu Herbert
Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii, USA.
Department of Surgical Sciences, Azienda Ospedaliero-Universitaria, Turin, Italy.
Oncotarget. 2015 Apr 20;6(11):8579-92. doi: 10.18632/oncotarget.3287.
LINC00472 is a novel long intergenic non-coding RNA. We evaluated LINC00472 expression in breast tumor samples using RT-qPCR, performed a meta-analysis of over 20 microarray datasets from the Gene Expression Omnibus (GEO) database, and investigated the effect of LINC00472 expression on cell proliferation and migration in breast cancer cells transfected with a LINC00472-expressing vector. Our qPCR results showed that high LINC00472 expression was associated with less aggressive breast tumors and more favorable disease outcomes. Patients with high expression of LINC00472 had significantly reduced risk of relapse and death compared to those with low expression. Patients with high LINC00472 expression also had better responses to adjuvant chemo- or hormonal therapy than did patients with low expression. Results of meta-analysis on multiple studies from the GEO database were in agreement with the findings of our study. High LINC00472 was also associated with favorable molecular subtypes, Luminal A or normal-like tumors. Cell culture experiments showed that up-regulation of LINC00472 expression could suppress breast cancer cell proliferation and migration. Collectively, our clinical and in vitro studies suggest that LINC00472 is a tumor suppressor in breast cancer. Evaluating this long non-coding RNA in breast tumors may have prognostic and predictive value in the clinical management of breast cancer.
LINC00472是一种新型的长链基因间非编码RNA。我们使用逆转录定量聚合酶链反应(RT-qPCR)评估了乳腺肿瘤样本中LINC00472的表达,对来自基因表达综合数据库(GEO)的20多个微阵列数据集进行了荟萃分析,并研究了LINC00472表达对转染了表达LINC00472载体的乳腺癌细胞增殖和迁移的影响。我们的qPCR结果表明,LINC00472高表达与侵袭性较低的乳腺肿瘤及更有利的疾病预后相关。与低表达患者相比,LINC00472高表达患者的复发和死亡风险显著降低。LINC00472高表达的患者对辅助化疗或激素治疗的反应也优于低表达患者。对GEO数据库中多项研究的荟萃分析结果与我们的研究结果一致。LINC00472高表达还与有利的分子亚型、管腔A型或正常样肿瘤相关。细胞培养实验表明,LINC00472表达上调可抑制乳腺癌细胞的增殖和迁移。总体而言,我们的临床和体外研究表明,LINC00472是乳腺癌中的一种肿瘤抑制因子。在乳腺肿瘤中评估这种长链非编码RNA可能对乳腺癌的临床管理具有预后和预测价值。