Exosomal microRNA miR-1246 induces cell motility and invasion through the regulation of DENND2D in oral squamous cell carcinoma.
Exosomal microRNA miR-1246 induces cell motility and invasion through the regulation of DENND2D in oral squamous cell carcinoma.
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DOI：
10.1038/srep38750
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发表时间：
2016-12-08
影响因子：
4.6
通讯作者：
Inazawa J
中科院分区：
文献类型：
--
作者：
Sakha S;Muramatsu T;Ueda K;Inazawa J
转移与癌症的不良预后相关。外泌体，这是挤满了RNA和蛋白质，并释放在所有的生物液体，正在成为一个重要的调解人的细胞间通讯。然而，外泌体在癌症转移中的功能仍然知之甚少。在这里，我们证明了通过尺寸排阻色谱法从高转移性人口腔癌细胞系HOC 313-LM中分离的外来体通过激活ERK和AKT诱导细胞生长，以及促进转移性差的癌细胞系HOC 313-P的细胞运动。MicroRNA（miRNA）阵列分析鉴定了两种致癌miRNA，miR-342- 3 p和miR-1246，在外泌体中高度表达。这些miRNAs通过exosomes转移到转移性差的细胞中，导致细胞运动性和侵袭能力增加。此外，miR-1246通过直接靶向含DENN/MADD结构域的2D（DEND 2D）来增加细胞运动性。总之，我们的研究结果支持外泌体和外泌体miRNA的转移作用，这突出了它们在基于miRNA的治疗中的应用潜力。
Metastasis is associated with poor prognosis in cancers. Exosomes, which are packed with RNA and proteins and are released in all biological fluids, are emerging as an important mediator of intercellular communication. However, the function of exosomes remains poorly understood in cancer metastasis. Here, we demonstrate that exosomes isolated by size-exclusion chromatography from a highly metastatic human oral cancer cell line, HOC313-LM, induced cell growth through the activation of ERK and AKT as well as promoted cell motility of the poorly metastatic cancer cell line HOC313-P. MicroRNA (miRNA) array analysis identified two oncogenic miRNAs, miR-342–3p and miR-1246, that were highly expressed in exosomes. These miRNAs were transferred to poorly metastatic cells by exosomes, which resulted in increased cell motility and invasive ability. Moreover, miR-1246 increased cell motility by directly targeting DENN/MADD Domain Containing 2D (DENND2D). Taken together, our findings support the metastatic role of exosomes and exosomal miRNAs, which highlights their potential for applications in miRNA-based therapeutics.
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DOI：
10.1158/1541-7786.mcr-14-0697
发表时间：
2015-09
期刊：
Molecular cancer research : MCR
影响因子：
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作者：
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通讯作者：
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