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Angiogenin promotes colorectal cancer metastasis via tiRNA production
Author(s) -
Li Siqi,
Shi Xiaoliang,
Chen Muxiong,
Xu Ningqin,
Sun Desen,
Bai Rongpan,
Chen Haiyan,
Ding Kefeng,
Sheng Jinghao,
Xu Zhengping
Publication year - 2019
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.32245
Subject(s) - angiogenin , metastasis , angiogenesis , colorectal cancer , cancer research , cancer , biology , downregulation and upregulation , cell growth , medicine , gene , genetics
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.