Exosome-mediated transfer of miR-1260b promotes cell invasion through Wnt/β-catenin signaling pathway in lung adenocarcinoma
Exosome-mediated transfer of miR-1260b promotes cell invasion through Wnt/β-catenin signaling pathway in lung adenocarcinoma
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外泌体介导的 miR-1260b 转移通过 Wnt/β-catenin 信号通路促进肺腺癌细胞侵袭
DOI：
10.1002/jcp.29578
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发表时间：
2020-02-05
影响因子：
5.6
通讯作者：
Chen, Liang
中科院分区：
文献类型：
--
作者：
Xia, Yang;Wei, Ke;Chen, Liang
越来越多的证据证实，外泌体介导的microrna转移可以通过细胞间通讯影响肿瘤的进展，包括肿瘤细胞侵袭、细胞增殖和耐药性。然而，外泌体mir -1260b在肺腺癌（LAC）中的潜在作用仍然知之甚少。因此，本研究重点研究外泌体mir -1260b在细胞侵袭中的功能。通过实时定量聚合酶链反应，发现LAC患者血浆中外泌体mir -1260b高于健康人。外泌体- mir -1260b的敏感性为72%，特异性为86%（截止点为2.027），曲线下面积为0.845 （95% CI = 0.772 ~ 0.922）。LAC组织中miR-1260b表达升高与血浆中外泌体miR-1260b表达升高呈正相关（r = 0.642, p < 0.05）。此外，神经酰胺生物合成调节外泌体mir -1260b的分泌。外泌体介导的miR-1260b转移促进了A549细胞的侵袭，并且在A549细胞内仍具有功能。此外，外泌体mir -1260b通过抑制sFRP1和Smad4调节Wnt/ β -catenin信号通路。本研究发现了一种通过外泌体介导的肿瘤细胞间通讯参与细胞侵袭的新调控机制。靶向外泌体micrornas可能为LAC的诊断和治疗提供新的见解。
Increasing evidence confirms that exosome-mediated transfer of microRNAs can influence cancer progression including tumor cell invasion, cell proliferation, and drug resistance via cell-cell communication. However, the potential role of exosomal-miR-1260b in lung adenocarcinoma (LAC) remains poorly understood. Thus, this study focused on investigating the function of exosomal-miR-1260b on cell invasion. Exosomal-miR-1260b was found to be higher in plasma of patients with LAC than that of healthy persons via quantitative real-time polymerase chain reaction assay. The sensitivity and specificity of exosomal-miR-1260b (cutoff point: 2.027) were 72% and 86%, and area under the curve of 0.845 (95% CI = 0.772-0.922). Elevated expression of miR-1260b in LAC tissues was positively correlated with exosomal-miR-1260b in plasma (r = .642, p < .05). Furthermore, ceramide biosynthesis regulated exosomal-miR-1260b secretion. Exosome-mediated transfer of miR-1260b promoted A549 cell invasion and was still functional inside A549 cells. Moreover, exosomal-miR-1260b regulated Wnt/beta-catenin signaling pathway by inhibiting sFRP1 and Smad4. This study identified a new regulation mechanism involving in cell invasion by exosome-mediated tumor-cell-to-tumor-cell communication. Targeting exosome-microRNAs may provide new insights into the diagnosis and treatment of LAC.