Akhavantabasi Shiva, Sapmaz Aysegul, Tuna Serkan, Erson-Bensan Ayse Elif
Department of Biological Sciences, M.E.T.U., Inonu Bulvari, Ankara 06531, Turkey.
Cell Struct Funct. 2012;37(1):27-38. doi: 10.1247/csf.11025.
Mounting evidence suggests involvement of deregulated microRNA (miRNA) expression during the complex events of tumorigenesis. Among such deregulated miRNAs in cancer, miR-125b expression is reported to be consistently low in breast cancers. In this study, we screened a panel of breast cancer cell lines (BCCLs) for miR-125b expression and detected decreased expression in 14 of 19 BCCLs. Due to the heterogeneity of breast cancers, MCF7 cells were chosen as a model system for ERBB2 independent breast cancers to restore miR-125b expression (MCF7-125b) to investigate the phenotypical and related functional changes. Earlier, miR-125b was shown to regulate cell motility by targeting ERBB2 in ERBB2 overexpressing breast cancer cells. Here we showed decreased motility and migration in miR-125b expressing MCF7 cells, independent of ERBB2. MCF7-125b cells demonstrated profoundly decreased cytoplasmic protrusions detected by phalloidin staining of filamentous actin along with decreased motility and migration behaviors detected by in vitro wound closure and transwell migration assays compared to empty vector transfected cells (MCF7-EV). Among possible numerous targets of miR-125b, we showed ARID3B (AT-rich interactive domain 3B) to be a novel target with roles in cell motility in breast cancer cells. When ARID3B was transiently silenced, the decreased cell migration was also observed. In light of these findings, miR-125b continues to emerge as an interesting regulator of cancer related phenotypes.
越来越多的证据表明，在肿瘤发生的复杂过程中，存在失调的微小RNA（miRNA）表达。在癌症中这类失调的miRNA中，据报道miR-125b在乳腺癌中的表达一直很低。在本研究中，我们筛选了一组乳腺癌细胞系（BCCLs）的miR-125b表达情况，在19个BCCLs中有14个检测到其表达降低。由于乳腺癌的异质性，选择MCF7细胞作为ERBB2非依赖性乳腺癌的模型系统，以恢复miR-125b表达（MCF7-125b），从而研究表型及相关功能变化。此前研究表明，在ERBB2过表达的乳腺癌细胞中，miR-125b通过靶向ERBB2来调节细胞运动。在此我们发现，在表达miR-125b的MCF7细胞中，细胞运动性和迁移能力降低，且与ERBB2无关。与空载体转染细胞（MCF7-EV）相比，MCF7-125b细胞经丝状肌动蛋白的鬼笔环肽染色检测显示，其细胞质突起明显减少，同时体外伤口愈合和Transwell迁移试验检测到其运动性和迁移行为也降低。在miR-125b可能的众多靶标中，我们发现富含AT互作结构域3B（ARID3B）是一个在乳腺癌细胞运动中起作用的新靶标。当ARID3B被瞬时沉默时，也观察到细胞迁移减少。鉴于这些发现，miR-125b持续成为癌症相关表型的一个有趣的调节因子。
