Discovery of antitumor effects of leczymes

Tatsuta, Takeo; Hosono, Masahiro

doi:10.1007/s10719-021-10033-9

Cited by 1 publication

(1 citation statement)

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“…However, many frog RNases are carbohydrate-binding enzymes [ 68 , 76 ], assigning them a double, RNase plus lectin, function [ 77 ]. This would suggest they are also leczymes that are known to display antitumor activity [ 78 ], not in contrast with the ability of ONC to bind sialic-acid molecules present on the surface of malignant cells in humans and to induce their deathful agglutination [ 79 ]. Indeed, although the physiological role of ONC in amphibians is not still precisely defined, its application in mammals, in humans in particular, has been extensively investigated.…”

Section: Rnases and Rna Processing As Tumor And Viral Infection Manag...mentioning

confidence: 99%

Role of the Ribonuclease ONCONASE in miRNA Biogenesis and tRNA Processing: Focus on Cancer and Viral Infections

Menegazzi

Gotte

2022

IJMS

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The majority of transcribed RNAs do not codify for proteins, nevertheless they display crucial regulatory functions by affecting the cellular protein expression profile. MicroRNAs (miRNAs) and transfer RNA-derived small RNAs (tsRNAs) are effectors of interfering mechanisms, so that their biogenesis is a tightly regulated process. Onconase (ONC) is an amphibian ribonuclease known for cytotoxicity against tumors and antiviral activity. Additionally, ONC administration in patients resulted in clinical effectiveness and in a well-tolerated feature, at least for lung carcinoma and malignant mesothelioma. Moreover, the ONC therapeutic effects are actually potentiated by cotreatment with many conventional antitumor drugs. This review not only aims to describe the ONC activity occurring either in different tumors or in viral infections but also to analyze the molecular mechanisms underlying ONC pleiotropic and cellular-specific effects. In cancer, data suggest that ONC affects malignant phenotypes by generating tRNA fragments and miRNAs able to downregulate oncogenes expression and upregulate tumor-suppressor proteins. In cells infected by viruses, ONC hampers viral spread by digesting the primer tRNAs necessary for viral DNA replication. In this scenario, new therapeutic tools might be developed by exploiting the action of ONC-elicited RNA derivatives.

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