Three decades of research on angiogenin: a review and perspective

Abstract

As a member of the vertebrate-specific secreted ribonucleases, angiogenin (ANG) was first isolated and identified solely by its ability to induce new blood vessel formation, and now, it has been recognized to play important roles in various physiological and pathological processes through regulating cell proliferation, survival, migration, invasion, and/or differentiation. ANG exhibits very weak ribonucleolytic activity that is critical for its biological functions, and exerts its functions through activating different signaling transduction pathways in different target cells. A series of recent studies have indicated that ANG contributes to cellular nucleic acid metabolism. Here, we comprehensively review the results of studies regarding the structure, mechanism, and function of ANG over the past three decades. Moreover, current problems and future research directions of ANG are discussed. The understanding of the function and mechanism of ANG in a wide context will help to better delineate its roles in diseases, especially in cancer and neurodegenerative diseases.

Evidence for Novel Action at the Cell‐Binding Site of Human Angiogenin Revealed by Heteronuclear NMR Spectroscopy, in silico and in vivo Studies

“…hAng seems to play key roles in a plethora of biological processes and is also implicated in almost every step of tumorigenesis. It has thus become a validated diagnostic tool, a prognosis and therapy‐monitoring marker in cancer for physicians, as well as a validated pharmaceutical target for the development of new anticancer agents…”

“…Angiogenin is an angiogenic factor, playing a major role in the growth and establishment of human tumors, whereas RNase A is not . In the extracellular environment, secreted hAng binds to a 170‐kDa transmembrane protein that has yet to be fully characterized, activating many signal transduction pathways . Extracellular hAng also interacts with cell‐surface actin, promoting extracellular matrix degradation, thus allowing cell migration and invasion .…”

“…In the extracellular environment, secreted hAng binds to a 170‐kDa transmembrane protein that has yet to be fully characterized, activating many signal transduction pathways . Extracellular hAng also interacts with cell‐surface actin, promoting extracellular matrix degradation, thus allowing cell migration and invasion . Under growth conditions hAng accumulates in the nucleus/nucleolus, promoting mRNA transcription and rRNA transcription/procession, while under stress conditions it accumulates in the cytoplasm, where it forms tiRNAs leading to the inhibition of translational initiation .…”

Angiogenin promotes colorectal cancer metastasis via tiRNA production

“…Angiogenin (ANG), a member of the ribonuclease A superfamily, contributes to tumor pathology by inducing angiogenesis and promoting tumor cell survival, growth and metastasis . Recent advances indicate that the subcellular localization and ribonucleolytic activity of ANG are essential to its biological functions .…”

The role of RNA modifications in the regulation of tRNA cleavage

“…Despite having high similarity to bovine pancreatic RNase A, it has significantly reduced activity due to occlusion of the active site by a glutamine residue not found in RNase A . ANG was discovered and characterized by its ability to promote new blood vessel growth , making it a potential anticancer therapeutic target . The ability of ANG to promote growth and angiogenesis is dependent upon its catalytic activity yet in vivo RNA targets of ANG were unknown until recently.…”