Angiogenin promotes colorectal cancer metastasis via tiRNA production
Angiogenin promotes colorectal cancer metastasis via tiRNA production
复制标题
血管生成素通过 tiRNA 产生促进结直肠癌转移
DOI：
10.1002/ijc.32245
复制
发表时间：
2019-09-01
影响因子：
6.4
通讯作者：
Xu, Zhengping
中科院分区：
文献类型：
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作者：
Li, Siqi;Shi, Xiaoliang;Xu, Zhengping
结直肠癌（CRC）的转移是CRC相关死亡的主要原因。血管生成素（Angiogenin，ANG）是核糖核酸酶A超家族成员之一，它不仅能激活内皮细胞诱导肿瘤血管生成，还能靶向肿瘤细胞，促进细胞存活、增殖和/或迁移。然而，其在结直肠癌转移中的临床意义和潜在机制仍不清楚。在这里，我们报道了ANG在结直肠癌组织中上调，并与结直肠癌患者的转移有关。然后，我们揭示了ANG在体外和体内系统中增强CRC生长和转移。有趣的是，我们表征了一系列tRNA衍生的应激诱导的小RNA（tiRNAs），其通过ANG切割产生，在CRC肿瘤组织和高转移性细胞中富集，并在ANG促进的CRC转移中起作用。此外，在CRC患者中观察到更高水平的来自成熟tRNA-Val的5 '-tiRNA（5 '-tiRNA-Val），并且与肿瘤转移相关。综上所述，我们认为一种新的ANG-tiRNAs-细胞迁移和侵袭调控轴促进结直肠癌转移，可能成为结直肠癌诊断和治疗的潜在靶点。
Metastasis of colorectal cancer (CRC) is the leading cause of CRC-associated mortality. Angiogenin (ANG), a member of the ribonuclease A superfamily, not only activates endothelial cells to induce tumor angiogenesis, but also targets tumor cells to promote cell survival, proliferation and/or migration. However, its clinical significance and underlying mechanism in CRC metastasis are still largely unknown. Here, we reported that ANG was upregulated in CRC tissues and associated with metastasis in CRC patients. We then revealed that ANG enhanced CRC growth and metastasis in both in vitro and in vivo systems. Intriguingly, we characterized a bunch of tRNA-derived stress-induced small RNAs (tiRNAs), produced through ANG cleavage, that was enriched in both CRC tumor tissues and highly metastatic cells, and functioned in ANG-promoted CRC metastasis. Moreover, higher level of a 5 '-tiRNA from mature tRNA-Val (5 '-tiRNA-Val) was observed in CRC patients and was correlated with tumor metastasis. Taken together, we propose that a novel ANG-tiRNAs-cell migration and invasion regulatory axis promotes CRC metastasis, which might be of potential target for CRC diagnosis and treatment.