The lncRNA H19 mediates breast cancer cell plasticity during EMT and MET plasticity by differentially sponging miR-200b/c and let-7b

Metastasis is a multistep process by which tumor cells disseminate from their primary site and form secondary tumors at a distant site. The pathophysiological course of metastasis is mediated by the dynamic plasticity of cancer cells, which enables them to shift between epithelial and mesenchymal phenotypes through a transcriptionally regulated program termed epithelial-to-mesenchymal transition (EMT) and its reverse process, mesenchymal-to-epithelial transition (MET). Using a mouse model of spontaneous metastatic breast cancer, we investigated the molecular mediators of metastatic competence within a heterogeneous primary tumor and how these cells then manipulated their epithelial-mesenchymal plasticity during the metastatic process. We isolated cells from the primary mammary tumor, the circulation, and metastatic lesions in the lung in TA2 mice and found that the long noncoding RNA (lncRNA) H19 mediated EMT and MET by differentially acting as a sponge for the microRNAs miR-200b/c and ...

肿瘤转移是一个多步骤进程，肿瘤细胞从原发部位播散，并在远端位点形成继发性肿瘤。肿瘤转移的病理生理过程由癌细胞的动态可塑性介导，癌细胞可通过转录调控程序在上皮表型与间质表型之间相互转换，该程序被称为上皮间质转化（epithelial-to-mesenchymal transition, EMT）及其逆过程间质上皮转化（mesenchymal-to-epithelial transition, MET）。本研究采用自发性转移性乳腺癌小鼠模型，探究了异质性原发肿瘤内转移潜能的分子介导机制，以及这些癌细胞在转移过程中如何调控其上皮间质可塑性。本研究从TA2小鼠的原发乳腺肿瘤、血液循环以及肺部转移灶中分离细胞，发现长链非编码RNA（long noncoding RNA, lncRNA）H19通过分别作为微小RNA（microRNA, miRNA）miR-200b/c的分子海绵来介导EMT与MET过程，以及……