Clinical relevance and functional significance of cell-free microRNA-1260b expression profiles in infiltrative myxofibrosarcoma
Clinical relevance and functional significance of cell-free microRNA-1260b expression profiles in infiltrative myxofibrosarcoma
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DOI：
10.1038/s41598-020-66120-8
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发表时间：
2020-06-10
影响因子：
4.6
通讯作者：
Ozaki, Toshifumi
中科院分区：
文献类型：
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作者：
Morita, Takuya;Fujiwara, Tomohiro;Ozaki, Toshifumi
浸润性肿瘤生长到邻近软组织是粘液纤维肉瘤（MFS）频繁复发和肿瘤相关死亡的主要原因，但没有有用的生物标志物反映肿瘤负荷和浸润性生长。虽然新出现的证据表明细胞外/循环microRNA（miRNA）在各种恶性疾病中的诊断和功能作用，但它们在MFS患者中的意义仍然未知。总体miRNA谱鉴定了MFS患者血清和MFS细胞培养基中四种上调的miRNA。其中，与健康个体区分的患者血清中血清miR-1260 b水平显着上调，并且与携带MFS小鼠的临床状态和肿瘤动力学密切相关。此外，血清中miR-1260 b的高表达与放射学尾样模式相关，这是浸润性MFS的特征。细胞外miR-1260 b嵌入肿瘤来源的细胞外囊泡（EV）中，并通过下调邻近正常成纤维细胞中的PCDH 9来促进MFS的细胞侵袭。总的来说，循环miR-1260 b表达可能代表了这种高度侵袭性肉瘤肿瘤监测的新诊断靶点。此外，EV-miR-1260 b可以作为传递信使到邻近细胞并介导MFS的浸润性生长，通过肿瘤细胞与其微环境之间的串扰为浸润性性质的机制提供了新的见解。
Infiltrative tumor growth into adjacent soft tissues is a major cause of the frequent recurrence and tumor-related death of myxofibrosarcoma (MFS), but no useful biomarkers reflecting tumor burden and infiltrative growth are available. While emerging evidence suggests a diagnostic and functional role of extracellular/circulating microRNA (miRNA) in various malignant diseases, their significance in MFS patients remains unknown. Global miRNA profiling identified four upregulated miRNAs in MFS patient sera and culture media of MFS cells. Among these, serum miR-1260b level was significantly upregulated in patient serum discriminating from healthy individuals and closely correlated with clinical status and tumor dynamics in MFS-bearing mice. In addition, high miR-1260b expression in serum was correlated with radiological tail-like patterns, characteristic of the infiltrative MFS. The extracellular miR-1260b was embedded in tumor-derived extracellular vesicles (EVs) and promoted cellular invasion of MFS through the downregulation of PCDH9 in the adjacent normal fibroblasts. Collectively, circulating miR-1260b expression may represent a novel diagnostic target for tumor monitoring of this highly aggressive sarcoma. Moreover, EV-miR-1260b could act as a transfer messenger to adjacent cells and mediate the infiltrative growth of MFS, providing new insights into the mechanism of infiltrative nature via crosstalk between tumor cells and their microenvironment.