Department of Medical Oncology, Central Hospital of Xuzhou, Affiliated Xuzhou Hospital, Medical College of Southeast University, Xuzhou, China.
Med Sci Monit. 2012 Aug;18(8):BR299-308. doi: 10.12659/msm.883262.
Recent studies have suggested that microRNA-10b (miR-10b) acts as a promoter of metastasis in breast cancer, although the underlying mechanism remains largely unknown. In this study, we provide the first evidence that E-cadherin (E-cad) is a potential target of miR-10b.
MATERIAL/METHOD: By applying gain-of-function and loss-of-function approaches in the metastatic breast cancer cell line MDA-MB-231, we demonstrated that miR-10b is necessary and sufficient to regulate the cellular expression of E-cad and in vitro tumor cell invasion.
Comparative expression analysis of miR-10b in benign breast lesions (N=16), primary breast cancers (N=21), and metastatic breast carcinomas (N=23) revealed that miR-10b transcription was uniquely up-regulated in metastatic cancers. The expression level of miR-10b positively correlated with tumor size, pathological grading, clinical staging, lymph node metastasis, Her2-positivity and tumor proliferation, but was negatively associated with estrogen receptor-positivity, progesterone receptor-positivity and E-cad mRNA and protein levels.
These findings indicate the existence of a novel E-cadherin-related mechanism by which miR-10b modulates breast cancer metastasis. In addition, miR-10b may be a useful biomarker of advanced progression and metastasis of breast cancer.
最近的研究表明，microRNA-10b（miR-10b）在乳腺癌中作为转移的促进因子起作用，尽管其潜在机制在很大程度上仍不清楚。在这项研究中，我们首次提供证据表明 E-钙黏蛋白（E-cad）是 miR-10b 的一个潜在靶标。
材料/方法：通过在转移性乳腺癌细胞系 MDA-MB-231 中应用功能获得和功能丧失方法，我们证明 miR-10b 是调节细胞中 E-cad 表达和体外肿瘤细胞侵袭所必需和充分的。
对 16 例良性乳腺病变、21 例原发性乳腺癌和 23 例转移性乳腺癌中 miR-10b 的表达进行比较分析表明，miR-10b 的转录在转移性癌症中独特地上调。miR-10b 的表达水平与肿瘤大小、病理分级、临床分期、淋巴结转移、Her2 阳性和肿瘤增殖呈正相关，而与雌激素受体阳性、孕激素受体阳性以及 E-cad mRNA 和蛋白水平呈负相关。
这些发现表明存在一种新型的 E-钙黏蛋白相关机制，miR-10b 通过该机制调节乳腺癌转移。此外，miR-10b 可能是乳腺癌晚期进展和转移的有用生物标志物。
