Tumor-derived exosomal miR-619-5p promotes tumor angiogenesis and metastasis through the inhibition of RCAN1.4
Tumor-derived exosomal miR-619-5p promotes tumor angiogenesis and metastasis through the inhibition of RCAN1.4
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DOI：
10.1016/j.canlet.2020.01.023
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发表时间：
2020-01-01
期刊：
影响因子：
9.7
通讯作者：
Rho, Jin Kyung
中科院分区：
文献类型：
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作者：
Kim, Dong Ha;Park, Sojung;Rho, Jin Kyung
肿瘤源性外泌体 (TEX) 含有丰富的 miRNA，可作为癌症诊断的新型非侵入性生物标志物，并在癌症进展中发挥作用。我们研究了影响非小细胞肺癌 (NSCLC) 癌症进展的外泌体 miRNA，并鉴定了相关的特定分子。我们发现 NSCLC 细胞释放的外泌体中的特定 miRNA 可以调节血管生成，其中 miR-619-5p 是最有效的诱导剂。 RCAN1.4 被确定为 miR-619-5p 的靶标，其抑制可促进血管生成。此外，抑制 RCAN1.4 会诱导 NSCLC 细胞增殖和转移。在NSCLC患者中，肿瘤中RCAN1.4的表达水平显着低于正常肺组织，而miR-619.5p的表达水平显着高于正常肺组织。从 NSCLC 患者血浆中分离的外泌体中，miR-619-5p 表达高于正常水平。最后，缺氧条件诱导 miR-619-5p 上传至 NSCLC 细胞衍生的外泌体中。我们的研究结果表明，外泌体miR-619-5p通过调节RCAN1.4促进NSCLC的生长和转移，并可以作为这些肺癌的诊断指标。
Tumor derived exosomes (TEXs) contain enriched miRNAs that act as novel non-invasive biomarkers for cancer diagnosis and play a role in cancer progression. We investigated the exosomal miRNAs that affect cancer progression in non-small cell lung cancer (NSCLC) and identified the specific molecules involved. We identified that specific miRNAs in NSCLC cell-released exosomes can modulate angiogenesis, among which miR-619-5p was the most potent inducer. RCAN1.4 was identified as a target of miR-619-5p and its suppression promoted angiogenesis. Furthermore, the suppression of RCAN1.4 induced cell proliferation and metastasis in NSCLC cells. In patients with NSCLC, the level of RCAN1.4 expression was significantly lower, and that of miR-619.5p significantly higher, in tumor than normal lung tissues. miR-619-5p expression was higher than normal in exosomes isolated from the plasma of NSCLC patients. Finally, hypoxic conditions induced miR-619-5p upload into NSCLC cell-derived exosomes. Our findings indicate that exosomal miR-619-5p promotes the growth and metastasis of NSCLCs by regulating RCAN1.4 and can serve as a diagnostic indicator for these lung cancers.