Zhang Yunkun, Guo Chunmei, Yang Siwen, Elkharti Maroua, Liu Rui, Sun Ming-Zhong, Liu Shuqing
Department of Biochemistry, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China.
Department of Pathology, The Second Affiliated Hospital of Dalian Medical University, Dalian 116023, China.
J Clin Med. 2023 Mar 24;12(7):2478. doi: 10.3390/jcm12072478.
Lymphatic metastasis is the most common form in breast cancer (BC) progression. Previously, we observed that lnc045874, a most conservative homology of Homo Sapiens NONHSAT021545 (lnc021545), miR-330-3p, and EREG may have some effects in mouse hepatocarcinoma cell lines with different lymphatic metastasis potentials. Through data from TCGA and GEO database analysis, we speculated that miR-330-3p might be a tumor promoter, while EREG could be a tumor suppressor in BC. MiR-330-3p was upregulated, while lnc021545 and EREG were downregulated in 50 BC tissues. MiR-330-3p advanced the metastatic behaviors of BC cells, whereas lnc021545 and EREG resulted in the opposite effects. The three molecules' expressions were correlated respectively and showed that miR-330-3p targeted lnc021545 and EREG to affect their expressions. Lnc021545/miR-330-3p axis affected BC metastasis by regulating EREG in epithelial-to-mesenchymal transition. In 50 BC patients, these three molecules and their cooperation are associated with aggressive tumor phenotypes, patient outcomes, and trastuzumab therapy. We finally discovered that lnc021545, miR-330-3p, and EREG formed a multi-gene co-regulation system that affected the metastasis of BC and the cooperation reflects the synergistic effects of the three molecules, recommending that their cooperation may provide a more accurate index for anti-metastasis therapeutic and prognostic evaluation of BC.
淋巴转移是乳腺癌（BC）进展中最常见的形式。此前，我们观察到lnc045874，即智人NONHSAT021545（lnc021545）、miR-330-3p和EREG的最保守同源物，可能在具有不同淋巴转移潜能的小鼠肝癌细胞系中发挥一些作用。通过对TCGA和GEO数据库数据的分析，我们推测miR-330-3p可能是一种肿瘤促进因子，而EREG可能是BC中的一种肿瘤抑制因子。在50例BC组织中，miR-330-3p上调，而lnc021545和EREG下调。miR-330-3p促进了BC细胞的转移行为，而lnc021545和EREG则产生相反的效果。这三种分子的表达分别相关，表明miR-330-3p靶向lnc021545和EREG以影响它们的表达。lnc021545/miR-330-3p轴通过在上皮-间质转化中调节EREG来影响BC转移。在50例BC患者中，这三种分子及其协同作用与侵袭性肿瘤表型、患者预后和曲妥珠单抗治疗相关。我们最终发现lnc021545、miR-330-3p和EREG形成了一个多基因共调节系统，影响BC的转移，且这种协同作用反映了这三种分子的协同效应，提示它们的协同作用可能为BC的抗转移治疗和预后评估提供更准确的指标。
