A novel immune resistance mechanism of melanoma cells controlled by the ADAR1 enzyme

Galore-Haskel, Gilli; Nemlich, Yael; Greenberg, Eyal; Ashkenazi, Shira; Hakim, Motti; Itzhaki, Orit; Shoshani, Noa; Shapira-Fromer, Ronnie; Ben-Ami, Eytan; Ofek, Efrat; Anafi, Liat; Besser, Michal J.; Schachter, Jacob; Markel, Gal

doi:10.18632/oncotarget.4905

Cited by 56 publications

(50 citation statements)

References 59 publications

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“…ADAR1 also suppresses the expression of many miRNAs, including the stem cell self-renewal-promoting miR-302 family of miRNAs, in an RNA editing-independent manner, which is essential for neural differentiation of human ES cells 121 . Editing-independent suppression of miR-222 expression by ADAR1 and the consequent upregulation of ICAM1, and the relevance of this to melanoma immune resistance, have also been reported 122 . Finally, global screening for ADAR1-binding sites suggested that ADAR1 might compete with DGCR8 for binding to many pri-miRNAs 123 .…”

Section: Editing Of Mirnas and Its Consequencesmentioning

confidence: 84%

A-to-I editing of coding and non-coding RNAs by ADARs

Nishikura

2015

Nat Rev Mol Cell Biol

815

854

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Adenosine deaminases acting on RNA (ADARs) convert adenosine to inosine in double-stranded RNA. This A-to-I editing occurs not only in protein-coding regions of mRNAs, but also frequently in non-coding regions that contain inverted Alu repeats. Editing of coding sequences can result in the expression of functionally altered proteins that are not encoded in the genome, whereas the significance of Alu editing remains largely unknown. Certain microRNA (miRNA) precursors are also edited, leading to reduced expression or altered function of mature miRNAs. Conversely, recent studies indicate that ADAR1 forms a complex with Dicer to promote miRNA processing, revealing a new function of ADAR1 in the regulation of RNA interference.

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Section: Editing Of Mirnas and Its Consequencesmentioning

confidence: 84%

A-to-I editing of coding and non-coding RNAs by ADARs

Nishikura

2015

Nat Rev Mol Cell Biol

815

854

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show abstract

“…Recently, it was demonstrated that ADAR1 participates in the regulation of miRNA biogenesis via base editing. The means by which ADAR1 regulates macrophage polarization and function has become an area of intensive research (47,48).…”

Section: Discussionmentioning

confidence: 99%

ADAR1 attenuates allogeneic graft rejection by suppressing miR‐21 biogenesis in macrophages and promoting M2 polarization

Liu¹,

Xie²,

Liu³

et al. 2018

FASEB j.

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ADAR1 (adenosine deaminase acting on double-stranded RNA 1) is an RNA-editing enzyme that mediates adenosine-to-inosine RNA editing events, an important post-transcriptional modification mechanism that can alter the coding properties of mRNA or regulate microRNA biogenesis. ADAR1 also regulates the innate immune response. Here, we have demonstrated that ADAR1 expression increased in LPS-stimulated macrophages. Silencing ADAR1 by using small interfering RNA in macrophages resulted in the pronounced polarization of macrophages to M1, whereas ADAR1 overexpression promoted M2 polarization, which indicated that ADAR1 can inhibit macrophage hyperpolarization and prevent immune hyperactivity. The RNA-RNP immunoprecipitation binding assay demonstrated a direct interaction between ADAR1 and miR-21 precursor. Significant up-regulation in IL-10 and down-regulation in miR-21 were observed in ADAR1-overexpressing macrophages. We evaluated miR-21 target mRNAs and macrophage polarization signaling pathways and found that forkhead box protein O1 (Foxo1) was up-regulated in cells that overexpressed ADAR1. In a mouse allogeneic skin transplantation model, grafts in the ADAR1-overexpressed group survived longer and suffered less immune cell infiltration. In ADAR1-overexpressed recipients, splenic macrophages were significantly polarized to M2, and levels of sera IL-10 were markedly higher than those in the control group. In summary, ADAR1 modulates macrophage M2 polarization via the ADAR1-miR-21-Foxo1-IL-10 axis, thereby suppressing allogeneic graft rejection.-Li, J., Xie, J., Liu, S., Li, X., Zhang, D., Wang, X., Jiang, J., Hu, W., Zhang, Y., Jin, B., Zhuang, R., Yin, W. ADAR1 attenuates allogeneic graft rejection by suppressing miR-21 biogenesis in macrophages and promoting M2 polarization.

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“…In another example, miR‐20b, ‐21 and ‐130b are upregulated in advanced CRC and inhibit PTEN expression, resulting in PD‐L1 overexpression . In addition, some miRNAs have been mentioned as possible biomarkers for immunotherapy …”

mentioning

confidence: 99%

“…(17) In addition, some miRNAs have been mentioned as possible biomarkers for immunotherapy. (18)(19)(20) Cancer tissues consist of cancer cells and surrounding stromal cells, including inflammatory cells, immunocompetent cells, endothelial cells, and fibroblasts. Stromal cells in the tumor microenvironment play an important role in cancer metastasis.…”

mentioning

confidence: 99%

miR‐125b‐1 and miR‐378a are predictive biomarkers for the efficacy of vaccine treatment against colorectal cancer

et al. 2017

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Many clinical trials of peptide vaccines have been conducted. However, these vaccines have provided clinical benefits in only a small fraction of patients. The purpose of the present study was to explore microRNAs (miRNAs) as novel predictive biomarkers for the efficacy of vaccine treatment against colorectal cancer. First, we carried out microarray analysis of pretreatment cancer tissues in a phase I study, in which peptide vaccines alone were given. Candidate miRNAs were selected by comparison of the better prognosis group with the poorer prognosis group. Next, we conducted microarray analysis of cancer tissues in a phase II study, in which peptide vaccines combined with chemotherapy were given. Candidate miRNAs were further selected by a similar comparison of prognosis. Subsequently, we carried out reverse‐transcription PCR analysis of phase II cases, separating cancer tissues into cancer cells and stromal tissue using laser capture microdissection. Treatment effect in relation to overall survival (OS) and miRNA expression was analyzed. Three miRNA predictors were negatively associated with OS: miR‐125b‐1 in cancer cells (P = 0.040), and miR‐378a in both cancer cells (P = 0.009) and stromal cells (P < 0.001). Multivariate analysis showed that expression of miR‐378a in stromal cells was the best among the three predictors (HR, 2.730; 95% CI, 1.027–7.585; P = 0.044). In conclusion, miR‐125b‐1 and miR‐378a expression might be considered as novel biomarkers to predict the efficacy of vaccine treatment against colorectal cancer.

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A novel immune resistance mechanism of melanoma cells controlled by the ADAR1 enzyme

Cited by 56 publications

References 59 publications

A-to-I editing of coding and non-coding RNAs by ADARs

A-to-I editing of coding and non-coding RNAs by ADARs

ADAR1 attenuates allogeneic graft rejection by suppressing miR‐21 biogenesis in macrophages and promoting M2 polarization

miR‐125b‐1 and miR‐378a are predictive biomarkers for the efficacy of vaccine treatment against colorectal cancer

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