Department of Gynecology, University Medical Center Hamburg-Eppendorf, Germany.
Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Germany.
Mol Oncol. 2019 May;13(5):1137-1149. doi: 10.1002/1878-0261.12472. Epub 2019 Mar 14.
Long noncoding RNAs (lncRNAs) are frequently precursor RNAs of microRNAs (miRNAs) or act as competing endogenous RNAs (ceRNAs) to interact with miRNAs. To better understand the shared impact of lncRNAs and miRNAs in the regulatory post-transcriptional network, we focused here on the relationships between (a) lncRNA H19 and miR-675, (b) NEAT1 and miR-204, and (c) HOTAIR and miR-331 in plasma of early breast cancer (BC) patients. We quantified each RNA in plasma samples of 63 BC patients and 10 healthy women by quantitative real-time PCR. In cell culture experiments, the influence of these noncoding RNAs (ncRNAs) on proliferation and apoptosis of BC cell line MCF-7 was examined. Plasma levels of H19 (P = 0.030), NEAT1 (P = 0.030), and miR-331 (P = 0.012) were deregulated in BC patients compared with healthy women. In both cohorts, the concentrations of H19 correlated with those of miR-675 (P = 0.0001). Higher H19 (P = 0.001) along with lower miR-675 (P = 0.007) levels and higher miR-204 (P = 0.017) along with lower NEAT1 (P = 0.030) levels were detected in plasma of HER2-positive patients compared with the other BC subgroups. Whereas the expression of HOTAIR was below the detection level, miR-331 levels correlated with nodal status (P = 0.002) and recurrence (P = 0.012). In cell culture experiments, a competitive impact on cell proliferation and apoptosis by these ncRNAs was also documented. Our findings describe a relationship of the plasma levels of H19/miR-675 and NEAT1/miR-204 in the different BC subtypes; in addition, they reveal an interplay between these lncRNAs and miRNAs in the regulatory network in MCF-7 cells, which should also be considered in the search for new diagnostic and therapeutic markers.
长链非编码 RNA (lncRNA) 通常是 microRNA (miRNA) 的前体 RNA，或者作为竞争性内源 RNA (ceRNA) 与 miRNA 相互作用。为了更好地理解 lncRNA 和 miRNA 在调控转录后网络中的共同作用，我们重点研究了（a）lncRNA H19 和 miR-675、（b）NEAT1 和 miR-204 以及（c）HOTAIR 和 miR-331 在早期乳腺癌 (BC) 患者血浆中的关系。我们通过定量实时 PCR 定量检测了 63 例 BC 患者和 10 例健康女性血浆样本中的每种 RNA。在细胞培养实验中，研究了这些非编码 RNA (ncRNA) 对 BC 细胞系 MCF-7 增殖和凋亡的影响。与健康女性相比，BC 患者血浆中 H19 (P=0.030)、NEAT1 (P=0.030) 和 miR-331 (P=0.012) 的水平失调。在两个队列中，H19 的浓度与 miR-675 的浓度相关 (P=0.0001)。与其他 BC 亚组相比，HER2 阳性患者的血浆中检测到更高的 H19 (P=0.001) 以及更低的 miR-675 (P=0.007) 水平和更高的 miR-204 (P=0.017) 以及更低的 NEAT1 (P=0.030) 水平。虽然 HOTAIR 的表达低于检测水平，但 miR-331 水平与淋巴结状态 (P=0.002) 和复发 (P=0.012) 相关。在细胞培养实验中，这些 ncRNA 对细胞增殖和凋亡也有竞争影响。我们的研究结果描述了 H19/miR-675 和 NEAT1/miR-204 在不同 BC 亚型中的血浆水平关系；此外，它们揭示了这些 lncRNA 和 miRNA 在 MCF-7 细胞调控网络中的相互作用，这也应该在寻找新的诊断和治疗标志物时加以考虑。
