Breast tissue-based microRNA panel highlights microRNA-23a and selected target genes as putative biomarkers for breast cancer
Breast tissue-based microRNA panel highlights microRNA-23a and selected target genes as putative biomarkers for breast cancer
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DOI：
10.1016/j.trsl.2014.10.001
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发表时间：
2015-03-01
影响因子：
7.8
通讯作者：
Shehata, Hanan H.
中科院分区：
文献类型：
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作者：
Eissa, Sanaa;Matboli, Marwa;Shehata, Hanan H.
我们探究了基于乳腺组织的微小核糖核酸（miRNAs）组合的差异表达及其作为乳腺癌（BC）预后标志物的潜在应用。本研究分为以下几个阶段：（1）基于微阵列特征谱（由miRWalk发布）检索出的6种乳腺癌特征性miRNAs组合，使用基于SYBR Green的聚合酶链反应（PCR）阵列在16例癌性和16例非癌性乳腺组织中进行探究；（2）关键miRNA靶基因的通路富集分析；（3）在更大的一组76例乳腺癌患者、36例乳腺良性疾病患者和36例健康志愿者中通过实时PCR进行标志物选择和验证；（4）通过常规逆转录酶（RT） - PCR验证miRNA（miR） - 23a靶基因（叉头框M（FOXM1）和富含组氨酸糖蛋白（HRG））；（5）探究所研究参数在乳腺癌验证组中的预后意义。在基于PCR阵列的miRNA表达分析中，发现4种miRNAs的变化超过两倍（miR - 96、miR - 29c、miR - 221和miR - 23a）。对靶基因的生物信息学分析显示在特殊的生物学过程类别上富集，即细胞周期、血管生成、细胞凋亡、细胞增殖和细胞黏附。在乳腺癌中，miR - 23a、HRG信使RNA和FOX信使RNA的阳性率分别为82.9%、72.4%和71.1%。miR - 23a与HRG和FOXM1组织RNAs之间的总体一致性率分别为91%和79%。中位随访期为49个月。mi - 23a和HRG RNA是无复发生存的重要独立预后标志物。miR - 23a可能具有致癌功能，并通过在RNA水平直接激活FOXM1和HRG促进乳腺癌进展。
We explored the differential expression of breast tissue-based panel of microRNAs (miRNAs) and their potential application as prognostic markers of breast cancer (BC). This study was divided into the following phases: (1) A panel of 6 BC characteristic miRNAs, which were retrieved based on the microarray signature profiling (released by miRWalk), was explored using SYBR Green-based polymerase chain reaction (PCR) array in 16 cancerous and 16 noncancerous breast tissue; (2) pathway enrichment analysis of the key miRNA target genes; (3) marker choice and validation by real-time PCR in a larger set of 76 patients with BC, 36 benign breast conditions, and 36 healthy volunteers; (4) validation of miRNA (miR)-23a target genes (forkhead box m (FOXM1) and histidine-rich glycoprotein (HRG)) by conventional reverse transcriptase (RT)-PCR; and (5) the prognostic significance of the investigated parameters in the BC validation group was explored. In PCR array-based miRNA expression analysis, 4 miRNAs were found to be altered more than twice (miR-96, miR-29c, miR-221, and miR-23a). Bioinformatic analysis of the target genes revealed enrichment for special biological process categories, that is, cell cycle, angiogenesis, apoptosis, cell proliferation, and cell adhesion. miR-23a, HRG messenger RNA, and FOX messenger RNA were positive in BC by 82.9%, 72.4%, and 71.1%, respectively. The overall concordance rates between miR-23a with HRG and FOXM1 tissue RNAs were 91% and 79%, respectively. The median follow-up period was 49 months. mi-23a and HRG RNA were significant independent prognostic markers in relapse-free survival. miR-23a may have an oncogenic function and enhance BC progression by directly activating FOXM1 and HRG at RNA level.