Sec23a mediates miR-200c augmented oligometastatic to polymetastatic progression.
Sec23a mediates miR-200c augmented oligometastatic to polymetastatic progression.
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Sec23a 介导 miR-200c 增强寡转移至多转移进展。
DOI：
10.1016/j.ebiom.2018.10.002
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发表时间：
2018-11
期刊：
影响因子：
11.1
通讯作者：
Rosie Xing H
中科院分区：
文献类型：
--
作者：
Sun Z;Zhou S;Tang J;Ye T;Li J;Liu D;Zhou J;Wang J;Rosie Xing H
癌症治疗基于肿瘤分期。治疗目的仅适用于局部肿瘤。最近的研究表明，转移数量有限的寡转移患者可能受益于针对转移的局部治疗，以实现长期生存。然而，寡转移到多转移进展的机制仍然难以捉摸。 miR-200c和Sec23a对肿瘤转移的影响在体外和体内均得到验证。通过质谱检测分泌蛋白组的变化。我们从人黑色素瘤癌细胞系 M14 建立了一对同源肺转移来源的寡转移和多转移细胞系。使用这两种细胞系，我们鉴定了 Sec23a（miR-200c 的基因靶标），通过其分泌组抑制 miR-200c 增强的寡转移至多转移进展。首先，miR-200c 过表达和 Sec23a 干扰加速了寡转移向多转移的进展。其次，Sec23a 在 miR-200c 下游发挥作用。第三，分泌蛋白谱的质谱分析表明，Sec23a 依赖性分泌蛋白组可能通过改变肿瘤微环境来影响转移定植。第四，使用癌症基因组图谱数据库进行的生存分析显示 Sec23a 是皮肤黑色素瘤的有利预后标志物，支持我们研究结果的临床相关性。 Sec23a 是寡转移到多转移进展的抑制剂这一发现具有临床意义。首先，它为开发预防寡转移到多转移的治疗方法提供了新的理论框架。其次，Sec23a 可用作有利的预后标志物，用于选择患有稳定寡转移疾病的患者进行基于寡转移的局部治疗。国家自然科学基金项目。
Cancer treatment is based on tumor staging. Curative intent is only applied to localized tumors. Recent studies show that oligometastatic patients who have limited number of metastases may benefit from metastasis-directed local treatments to achieve long-term survival. However, mechanisms underlying oligometastatic to polymetastatic progression remains elusive. The effects of miR-200c and Sec23a on tumor metastasis were verified both in vitro and in vivo. The secretome changes were detected by mass spectrometry. We established a pair of homologous lung-metastasis derived oligometastatic and polymetastatic cell lines from human melanoma cancer cell line M14. Using the two cell lines, we have identified Sec23a, a gene target of miR-200c, suppresses miR-200c augmented oligometastatic to polymetastatic progression via its secretome. Firstly, miR-200c over-expression and Sec23a interference accelerated oligometastatic to polymetatic progression. Secondly, Sec23a functions downstream of miR-200c. Thirdly, mass spectrometric analysis of the secretory protein profile suggests that Sec23a-dependent secretome may impact metastatic colonization by modifying tumor microenvironment. Fourthly, the survival analysis using The Cancer Genome Atlas database shows Sec23a as a favorable prognostic marker for skin cutaneous melanoma, supporting the clinical relevance of our findings. The finding that Sec23a is a suppressor of oligometastatic to polymetastatic progression has clinical implications. First, it provides a new theoretical framework for the development of treatments that prevent oligometastasis to polymetastasis. Second, Sec23a may be used as a favorable prognostic marker for the selection of patients with stable oligometastatic disease for oligometastasis-based local therapies of curative intent. National Natural Science Foundations of China.
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