RNase T2 in Inflammation and Cancer: Immunological and Biological Views

Wu, Lei; Xu, Yanquan; Zhao, Huakan; Li, Yongsheng

doi:10.3389/fimmu.2020.01554

Cited by 19 publications

(17 citation statements)

References 95 publications

(121 reference statements)

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“…RNASET2 belongs to the T2 family ribonucleases, which are highly conserved, since they are found in the genomes of protozoans, plants, bacteria, animals, and viruses [ 17 ]. Besides its nuclease activity, RNASET2 exerts many additional functions and it has been involved in several human pathologies, including inflammation and cancer [ 18 ]. RNASET2 has been associated with anti-tumor activities, since its overexpression is a good prognostic index in several neoplastic diseases [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

“…The role of RNASET2 is not restricted to cancer cells and could be relevant also in other cell types which are important players in the TME. In fact, RNASET2 has been recently associated with immune cell functions, highlighting its potential involvement in innate and, so far, anti-tumor immunity [ 18 , 23 , 24 , 25 ]. Thus, the modulation of RNASET2 expression and secretion in DCs may be functionally relevant in the TME.…”

Section: Introductionmentioning

confidence: 99%

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Hypoxia Enhances the Expression of RNASET2 in Human Monocyte-Derived Dendritic Cells: Role of PI3K/AKT Pathway

Monaci

Coppola

Giuntini

et al. 2021

IJMS

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Hypoxia is a key component of the tumor microenvironment (TME) and promotes not only tumor growth and metastasis, but also negatively affects infiltrating immune cells by impairing host immunity. Dendritic cells (DCs) are the most potent antigen-presenting cells and their biology is weakened in the TME in many ways, including the modulation of their viability. RNASET2 belongs to the T2 family of extracellular ribonucleases and, besides its nuclease activity, it exerts many additional functions. Indeed, RNASET2 is involved in several human pathologies, including cancer, and it is functionally relevant in the TME. RNASET2 functions are not restricted to cancer cells and its expression could be relevant also in other cell types which are important players in the TME, including DCs. Therefore, this study aimed to unravel the effect of hypoxia (2% O2) on the expression of RNASET2 in DCs. Here, we showed that hypoxia enhanced the expression and secretion of RNASET2 in human monocyte-derived DCs. This paralleled the HIF-1α accumulation and HIF-dependent and -independent signaling, which are associated with DCs’ survival/autophagy/apoptosis. RNASET2 expression, under hypoxia, was regulated by the PI3K/AKT pathway and was almost completely abolished by TLR4 ligand, LPS. Taken together, these results highlight how hypoxia- dependent and -independent pathways shape RNASET2 expression in DCs, with new perspectives on its implication for TME and, therefore, in anti-tumor immunity.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Hypoxia Enhances the Expression of RNASET2 in Human Monocyte-Derived Dendritic Cells: Role of PI3K/AKT Pathway

Monaci

Coppola

Giuntini

et al. 2021

IJMS

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show abstract

“…Interestingly, the RNases of the T2 family, present in bacteria, plants, viruses and also in animals [ 61 ], have their human version, called RNASET2, that is secreted by damaged tissues to initiate immune response [ 62 ].…”

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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“…For instance, the human RNASET2 tumor suppressor gene has been associated with RA development in Asian populations (52). This gene encodes for ribonuclease T2, an enzyme implicated in cancer development, and recently shown to regulate the innate immune response (e.g., macrophage function), which is implicated in RA development (53,54). Importantly, besides disease susceptibility, some of the non-HLA genes have also been associated with severity (55,56) and differences in seropositive and seronegative RA (31,57).…”

Section: Genetic Factorsmentioning

confidence: 99%

Etiology and Risk Factors for Rheumatoid Arthritis: A State-of-the-Art Review

Romão

Fonseca

2021

Front. Med.

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Rheumatoid arthritis (RA) is the most common systemic inflammatory rheumatic disease. It is associated with significant burden at the patient and societal level. Extensive efforts have been devoted to identifying a potential cause for the development of RA. Epidemiological studies have thoroughly investigated the association of several factors with the risk and course of RA. Although a precise etiology remains elusive, the current understanding is that RA is a multifactorial disease, wherein complex interactions between host and environmental factors determine the overall risk of disease susceptibility, persistence and severity. Risk factors related to the host that have been associated with RA development may be divided into genetic; epigenetic; hormonal, reproductive and neuroendocrine; and comorbid host factors. In turn, environmental risk factors include smoking and other airborne exposures; microbiota and infectious agents; diet; and socioeconomic factors. In the present narrative review, aimed at clinicians and researchers in the field of RA, we provide a state-of-the-art overview of the current knowledge on this topic, focusing on recent progresses that have improved our comprehension of disease risk and development.

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RNase T2 in Inflammation and Cancer: Immunological and Biological Views

Cited by 19 publications

References 95 publications

Hypoxia Enhances the Expression of RNASET2 in Human Monocyte-Derived Dendritic Cells: Role of PI3K/AKT Pathway

Hypoxia Enhances the Expression of RNASET2 in Human Monocyte-Derived Dendritic Cells: Role of PI3K/AKT Pathway

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

Etiology and Risk Factors for Rheumatoid Arthritis: A State-of-the-Art Review

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