Angiogenin promotes colorectal cancer metastasis via tiRNA production.

Abstract

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.

• Authors: Siqi Li, Xiaoliang Shi, Muxiong Chen, Ningqin Xu, Desen Sun, Rongpan Bai, Haiyan Chen, Kefeng Ding, Jinghao Sheng, Zhengping Xu
• Journal: International journal of cancer (Int J Cancer) Vol. 145 Issue 5 Pg. 1395-1407 (09 01 2019) ISSN: 1097-0215 [Electronic] United States
• PMID: 30828790 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 UICC.

Chemical References

• 5' Untranslated Regions
• RNA, Transfer
• angiogenin
• Ribonuclease, Pancreatic

Topics

• 5' Untranslated Regions
• Animals
• Case-Control Studies
• Cell Movement (physiology)
• Colonic Neoplasms (blood supply, genetics, metabolism, pathology)
• Gene Knockout Techniques
• Heterografts
• Humans
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Inbred NOD
• Mice, Nude
• Mice, SCID
• Neoplasm Invasiveness
• Neoplasm Metastasis
• Neovascularization, Pathologic (genetics, metabolism, pathology)
• RNA, Transfer (biosynthesis, genetics, metabolism)
• Ribonuclease, Pancreatic (genetics, metabolism)
• Up-Regulation