radART-Institute for Research and Development on Advanced Radiation Technologies, Paracelsus Medical University, Salzburg, Austria.
Department of Pathology, Paracelsus Medical University, SALK, Salzburg, Austria.
Breast Cancer. 2022 Mar;29(2):274-286. doi: 10.1007/s12282-021-01308-y. Epub 2021 Dec 5.
MicroRNAs are small non-coding RNAs with pivotal regulatory functions in multiple cellular processes. Their significance as molecular predictors for breast cancer was demonstrated in the past 15 years. The aim of this study was to elucidate the role of hsa-miR-3651 for predicting of local control (LC) in early breast cancer.
By means of high-throughput technology, hsa-miR-3651 was found to be differentially expressed between patients who experienced local relapse compared to those without (N = 23; p = 0.0035). This result could be validated in an independent cohort of 87 patients using RT-qPCR (p < 0.0005). In a second analysis step with a chip-based microarray containing 70,523 probes of potential target molecules, FERM domain protein 3 (FRMD3) was found to be the most down-regulated protein (N = 21; p = 0.0016). Computational analysis employing different prediction algorithms revealed FRMD3 as a likely downstream target of hsa-miR-3651 with an 8mer binding site between the two molecules. This could be validated in an independent patient set (N = 20, p = 0.134).
The current study revealed that hsa-miR-3651 is a predictor of LC in early breast cancer via its putative target protein FRMD3. Since microRNAs interfere in multiple pathways, the results of this hypothesis generating study may contribute to the development of tailored therapies for breast cancer in the future.
microRNAs 是具有多种细胞过程关键调节功能的小非编码 RNA。在过去的 15 年中,它们作为乳腺癌分子预测因子的重要性得到了证明。本研究的目的是阐明 hsa-miR-3651 在预测早期乳腺癌局部控制(LC)中的作用。
通过高通量技术,发现 hsa-miR-3651 在经历局部复发的患者与未经历局部复发的患者之间存在差异表达(N=23;p=0.0035)。这一结果可以在包含 87 例患者的独立队列中使用 RT-qPCR 进行验证(p<0.0005)。在第二个基于芯片的微阵列分析步骤中,该微阵列包含 70523 个潜在靶分子的探针,发现 FERM 结构域蛋白 3(FRMD3)是下调最明显的蛋白(N=21;p=0.0016)。采用不同预测算法的计算分析显示,FRMD3 是 hsa-miR-3651 的一个可能下游靶标,这两个分子之间存在 8 个碱基对的结合位点。这可以在一个独立的患者队列中进行验证(N=20,p=0.134)。
本研究揭示了 hsa-miR-3651 通过其假定的靶蛋白 FRMD3 成为早期乳腺癌 LC 的预测因子。由于 microRNAs 干扰多个途径,因此这项假设产生研究的结果可能有助于未来为乳腺癌开发定制治疗方法。