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评估 microRNAs 和两个靶基因 FOXO3a 和 RUNX2 的表达谱,可有效支持乳腺癌的诊断和治疗预测。

Evaluation of expression profiles of microRNAs and two target genes, FOXO3a and RUNX2, effectively supports diagnostics and therapy predictions in breast cancer.

出版信息

Neoplasma. 2016;63(6):941-951. doi: 10.4149/neo_2016_613.

Abstract

Breast cancer (BC) including its progression into bone metastasis is a complex process involving changes in gene expression and function of both, microRNAs (miRNAs) and their target genes. Deregulation of miRNAs has been described as a crucial factor responsible for the initiation and progression of BC, and specific miRNA expression profiles have been found to be associated with particular disease states, histological tumor types, and BRCA1/2 or HER status. BRCA1 tumor suppressor is involved in DNA damage response and repair and epigenetically controls miR-155 expression and its pre-cancerous potential. MiR-155 targets 3´UTR region of multiple components of the pro-oncogenic signaling cascades, including FOXO3a tumor suppressor and RUNX2 transcription factor regulating metastatic potential in BC. We employed qRT-PCR to determine expression level and examine possible regulatory role of selected miRNAs (miR-17, miR-18a, miR-19a, miR-20a, miR-21, miR-27a and miR-155) and their impact on expression modulation of FOXO3a and RUNX2 in peripheral blood mononuclear cells (PBMCs) in healthy individuals, in women carrying BRCA1 mutations with no disease manifestation, in women carrying BRCA1 mutations after tumor resection and therapy and in women with BC of unknown BRCA1 status in acute stage before tumor resection. Our results showed significant increase of miR-17, miR-19a, miR-21, miR-27, miR-155 and RUNX2 expression in PBMCs in BRCA1 patients and patients in acute stage, while FOXO3a expression was significantly decreased in these patients. MiR-18a and miR-20a expression was not affected. We propose that expressional changes reported in this study could provide significant additive information for early BC diagnosis, disease development prediction and therapy outcome monitoring.

摘要

乳腺癌(BC)包括其向骨转移的进展是一个涉及基因表达和功能变化的复杂过程,其中包括 microRNAs(miRNAs)及其靶基因。miRNA 的失调已被描述为导致 BC 发生和进展的关键因素,并且特定的 miRNA 表达谱与特定的疾病状态、组织学肿瘤类型以及 BRCA1/2 或 HER 状态相关。BRCA1 肿瘤抑制因子参与 DNA 损伤反应和修复,并通过表观遗传控制 miR-155 的表达及其癌前潜能。miR-155 靶向多个致癌信号级联的 3'UTR 区域,包括 FOXO3a 肿瘤抑制因子和 RUNX2 转录因子,调节 BC 的转移潜能。我们采用 qRT-PCR 来确定表达水平,并研究选定 miRNA(miR-17、miR-18a、miR-19a、miR-20a、miR-21、miR-27a 和 miR-155)的可能调节作用及其对健康个体外周血单个核细胞(PBMC)中 FOXO3a 和 RUNX2 表达调节的影响,在没有疾病表现的携带 BRCA1 突变的女性中,在肿瘤切除和治疗后携带 BRCA1 突变的女性中,以及在肿瘤切除前急性阶段未知 BRCA1 状态的 BC 女性中。我们的结果表明,在 BRCA1 患者和急性阶段患者的 PBMC 中,miR-17、miR-19a、miR-21、miR-27、miR-155 和 RUNX2 的表达显著增加,而这些患者的 FOXO3a 表达显著降低。miR-18a 和 miR-20a 的表达不受影响。我们提出,本研究中报道的表达变化可能为早期 BC 诊断、疾病发展预测和治疗结果监测提供重要的附加信息。

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