Oxidized low density lipoprotein receptor 1 promotes lung metastases of osteosarcomas through regulating the epithelial-mesenchymal transition
Oxidized low density lipoprotein receptor 1 promotes lung metastases of osteosarcomas through regulating the epithelial-mesenchymal transition
复制标题
氧化型低密度脂蛋白受体1通过调节上皮间质转化促进骨肉瘤肺转移
DOI：
10.1186/s12967-019-2107-9
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发表时间：
2019-11-12
影响因子：
7.4
通讯作者：
Luo, Qingquan
中科院分区：
文献类型：
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作者：
Jiang, Long;Jiang, Shanshan;Luo, Qingquan
氧化性低密度脂蛋白受体1 （OLR1）是一种II型膜蛋白，被认为是氧化性低密度脂蛋白的受体。本研究首次证明OLR1调节EMT，从而促进骨肉瘤（OS）的肺转移。方法所有相关实验均按生产厂家规定进行。体内肿瘤异种移植实验在6- 16周龄小鼠中进行，然后根据机构指南和当地当局批准在我们的动物设施中进行无病原体条件下的维持。为了研究目的而使用临床材料，事先获得了患者的同意和研究所研究伦理委员会的批准。所有统计分析均使用IBM SPSS Statistics 22.0 for Windows进行。结果采用微阵列技术探讨肿瘤转移相关的表观遗传机制。在26890个差异表达基因中鉴定出11个基因。在配对的原发组织和转移组织中验证后，本研究选择了OLR1。在4种常用细胞系中检测了OLR1的表达水平。过表达OLR1可增强细胞的增殖、迁移和侵袭能力。OLR1过表达也触发细胞周期G1至S + G2期。因此，当OLR1被沉默时，细胞的增殖、迁移和侵袭都会减少。olr1沉默阻断细胞周期G1至S + G2期。此外，OLR1沉默在体内有效抑制肿瘤的局部癌变和肺转移。此外，沉默OLR1抑制了间充质标志物（Snail、Twist和N-cadherin）的表达，但诱导了上皮标志物（E-cadherin）的表达。结论本研究提示了OLR1参与骨肉瘤肺转移的新的分子机制，强化了OLR1与骨肉瘤肺转移的相关性。
Background Oxidized low density lipoprotein receptor 1 (OLR1), a type II membrane protein, has been identified as receptor for oxidized low-density lipoprotein. The current study firstly provided evidence that OLR1 regulated EMT and thus promoted lung metastases in osteosarcoma (OS). Method All relevant experiments were conducted according to the manufacturer's protocols. In vivo tumor xenograft experiments were carried out in 6- to 16-week-old mice, then maintained in our animal facility under pathogen-free conditions in accordance with the Institutional Guidelines and approval by local authorities. For the use of the clinical materials for research purposes, prior patient's consent and approval from the Institute Research Ethics Committee were obtained. All statistical analyses were performed using IBM SPSS Statistics 22.0 for Windows. Result Microarrays were adopted to explore the underlying epigenetic mechanisms related to metastasis. 11 genes were identified among total 26,890 differentially expressed genes. After validated in paired primary and metastatic tissues, OLR1 was selected in the current study. The expression levels of OLR1 were tested in 4 widely used cell lines. Cell proliferation, migration and invasion could be enhanced when OLR1 was overexpressed. OLR1 overexpression also triggered G1 to S + G2 phases of cell cycle. Accordingly, cell proliferations, migration and invasion would be reduced when OLR1 was silenced. OLR1-silencing blocked G1 to S + G2 phases of cell cycle. Also, OLR1 silencing effectively suppressed local tumor carcinogenesis and lung metastases in vivo. Moreover, silencing OLR1 repressed the expression of mesenchymal markers (Snail, Twist, and N-cadherin), but induced an epithelial marker (E-cadherin). Conclusion This study indicated a novel molecular mechanism involving the role of OLR1 in lung metastases of osteosarcoma, strengthened the correlation between OLR1 and lung metastases.