Laboratorio de Oncología Molecular y Nuevos Blancos Terapéuticos, Instituto de Biología y Medicina Experimental (IBYME), CONICET, Buenos Aires C1428ADN, Argentina.
Department of Pathology and Cell Biology, Columbia University Medical Center, 630 W. 168th Street, New York, NY 10032, USA.
Int J Mol Sci. 2021 Oct 15;22(20):11135. doi: 10.3390/ijms222011135.
Breast cancer (BCa) is the leading cause of death by cancer in women worldwide. This disease is mainly stratified in four subtypes according to the presence of specific receptors, which is important for BCa aggressiveness, progression and prognosis. MicroRNAs (miRNAs) are small non-coding RNAs that have the capability to modulate several genes. Our aim was to identify a miRNA signature deregulated in preclinical and clinical BCa models for potential biomarker discovery that would be useful for BCa diagnosis and/or prognosis. We identified hsa-miR-21-5p and miR-106b-5p as up-regulated and hsa-miR-205-5p and miR-143-3p as down-regulated in BCa compared to normal breast or normal adjacent (NAT) tissues. We established 51 shared target genes between hsa-miR-21-5p and miR-106b-5p, which negatively correlated with the miRNA expression. Furthermore, we assessed the pathways in which these genes were involved and selected 12 that were associated with cancer and metabolism. Additionally, , , , , , , and were downregulated in BCa compared to NAT. Interestingly, hsa-miR-106b-5p was up-regulated, while , , and were downregulated in aggressive subtypes. Finally, patients with high levels of hsa-miR-106b-5 and low levels of the abovementioned genes had worse relapse free survival and worse overall survival, except for .
乳腺癌(BCa)是全球女性癌症死亡的主要原因。根据特定受体的存在,这种疾病主要分为四个亚型,这对于 BCa 的侵袭性、进展和预后很重要。微小 RNA(miRNA)是一种小的非编码 RNA,具有调节多个基因的能力。我们的目的是鉴定在临床前和临床 BCa 模型中失调的 miRNA 特征,以发现潜在的生物标志物,这将有助于 BCa 的诊断和/或预后。与正常乳腺或正常相邻(NAT)组织相比,我们发现 hsa-miR-21-5p 和 miR-106b-5p 在 BCa 中上调,而 hsa-miR-205-5p 和 miR-143-3p 下调。我们在 hsa-miR-21-5p 和 miR-106b-5p 之间建立了 51 个共享靶基因,这些靶基因与 miRNA 的表达呈负相关。此外,我们评估了这些基因参与的途径,并选择了 12 个与癌症和代谢有关的途径。此外,与 NAT 相比,在 BCa 中下调了 、 、 、 、 、 。有趣的是,hsa-miR-106b-5p 在侵袭性亚型中上调,而 、 、 、 下调。最后,hsa-miR-106b-5 水平高而上述基因水平低的患者无复发生存期和总生存期较差,除了 。