Exosomal miR-675 from metastatic osteosarcoma promotes cell migration and invasion by targeting CALN1
Exosomal miR-675 from metastatic osteosarcoma promotes cell migration and invasion by targeting CALN1
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来自转移性骨肉瘤的外泌体 miR-675 通过靶向 CALN1 促进细胞迁移和侵袭
DOI：
10.1016/j.bbrc.2018.04.016
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发表时间：
2018-06-02
影响因子：
3.1
通讯作者：
Shen, Yuhui
中科院分区：
文献类型：
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作者：
Gong, Liangzhi;Bao, Qiyuan;Shen, Yuhui
据报道，外泌体微小RNA（miRNAs）从肿瘤转移到基质细胞与各种上皮癌中的癌症进展和转移相关。然而，外泌体miRNA在骨肉瘤（OS）（最常见的骨恶性肿瘤）转移中的作用仍然很大程度上未知。在这项研究中，我们从细胞培养基和患者血清中纯化了中位尺寸接近100 nm的外泌体，并证明来源于转移性OS细胞而不是非转移性OS细胞的外泌体增加了非恶性成纤维细胞的迁移和侵袭。体外细胞（hFOB1.19）。此外，通过小RNA测序和RT-PCR验证鉴定了转移性和非转移性OS之间的差异miRNA货物，我们发现与非转移性对应物相比，转移性OS细胞系中的外泌体而非细胞miR-675水平高表达。同时，我们还发现外泌体miR-675可以下调受体细胞中CALN 1的表达，从而影响hF 0131. 19的侵袭和迁移。最后，还发现肿瘤标本中血清外泌体miR-675的上调和CALN 1的下调与OS患者的转移表型相关。我们的研究结果表明，外泌体miR-675是与OS相关的基因，血清外泌体miR-675表达可能作为OS转移的新生物标志物。（C）2018 Elsevier Inc. All rights reserved.
Exosomal microRNAs(miRNAs) transfer from tumor to stromal cells is reportedly associated with cancer progression and metastasis in various epithelial cancers. However, the role of exosomal miRNA in the metastasis of osteosarcoma(OS) -the most common bone malignancy-still largely remains unknown. In this study, we purified exosomes with a median size close to 100 nm from cell culture media as well as patient serum, and proved that exosomes derived from the metastatic, but not the non-metastatic OS cells increase the migration and invasion of non-malignant fibroblast cells (hFOB1.19) in vitro. Furthermore, the differential miRNA cargo between metastatic and non-metastatic OS is identified by small RNA sequencing and RT-PCR validation, we found a highly expression of exosomal, but not cellular miR-675 level in the metastatic OS cell-lines compared with non-metastatic counterparts. Meanwhile, we also found that exosomal miR-675 could down-regulate CALN1 expression in recipient cell, which may influence the invasion and migration of hF0131.19. Finally, the up regulation serum exosomal miR-675 and down regulation of CALN1 in tumor specimen was also found to be associated with the metastatic phenotype in OS patients. Our findings indicate that the exosomal miR-675 is a gene associated with OS and serum exosomal miR-675 expression may serve as a novel biomarker for the metastasis of OS. (C) 2018 Elsevier Inc. All rights reserved.