miR‐155: an ancient regulator of the immune system

Vigorito, Elena; Kohlhaas, Susan; Lu, Dong; Leyland, Rebecca

doi:10.1111/imr.12057

Cited by 265 publications

(229 citation statements)

References 116 publications

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“…MiR-155 has been extensively described for its essential role in the normal immune function of B-cell and T-cell lymphocytes and dendritic cells, but also as a likely driver in some aggressive lymphomas such as Hodgkin's and diffuse large B-cell (Vigorito et al 2013;Seddiki et al 2014). It has been proposed that because miR-155 is oncogenic in lympho-proliferative disorders, this may be true for other cancers.…”

Section: Introductionmentioning

confidence: 99%

Double-stranded microRNA mimics can induce length- and passenger strand–dependent effects in a cell type–specific manner

Goldgraben

Russell

Rueda

et al. 2015

RNA

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MicroRNAs are short (17-26) noncoding RNAs driving or modulating physiological and pathological cellular events. Overexpression of miR-155 is pathogenic in B-cell malignancy but was also reported in a number of solid tumors-in particular, in breast cancer, where its role remains unclear and often contradictory. Using representative cell line models, we sought to determine whether the discrepant miR-155 effects in breast cancer could be explained by the heterogeneity of the disease. The growth of six breast cancer cell lines transfected with several miRNA mimics was analyzed. We found MCF-7 cell growth to be inhibited by miR-155 and miR-145 mimics, both 23-nt long, but not by a number of shorter mimics, including a universal commercial negative control. Microarray and Western blot analyses revealed induction of apoptosis, associated with interferon-β after activation of the double-stranded RNA sensor pathway. 3 ′ Trimming of the miRNA mimics to 21 nt substantially reduced their growth-inhibitory potency. Mutating the canonical seed of the miR-155 mimic had no effect on the induced inhibition, which was abolished by mutating the miRNA seed of the artificial passenger strand. A panel of breast cancer cell lines showed a wide range of sensitivities to 23-mer mimics, broadly consistent with the sensitivity of the cell lines to Poly (I:C). We demonstrate two sources for nonspecific in vitro effects by miRNA mimics: duplex length and the artificial passenger strand. We highlight the danger of a universal 21-mer negative control and the importance of using matched seed mutants for reliable interpretation of phenotypes.

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Section: Introductionmentioning

confidence: 99%

Double-stranded microRNA mimics can induce length- and passenger strand–dependent effects in a cell type–specific manner

Goldgraben

Russell

Rueda

et al. 2015

RNA

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“…Recently, microRNA-155 (miR-155) has emerged as a central regulator of immune system homeostasis and inflammatory responses to pathogens and tumors (15,16). miR-155 is required for plasma cell differentiation (17) and dendritic cell activity (18).…”

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confidence: 99%

miR-155 augments CD8 ⁺ T-cell antitumor activity in lymphoreplete hosts by enhancing responsiveness to homeostatic γ _c cytokines

Ji¹,

Wrzesinski

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

103

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Lymphodepleting regimens are used before adoptive immunotherapy to augment the antitumor efficacy of transferred T cells by removing endogenous homeostatic "cytokine sinks." These conditioning modalities, however, are often associated with severe toxicities. We found that microRNA-155 (miR-155) enabled tumorspecific CD8 + T cells to mediate profound antitumor responses in lymphoreplete hosts that were not potentiated by immune-ablation. miR-155 enhanced T-cell responsiveness to limited amounts of homeostatic γc cytokines, resulting in delayed cellular contraction and sustained cytokine production. miR-155 restrained the expression of the inositol 5-phosphatase Ship1, an inhibitor of the serinethreonine protein kinase Akt, and multiple negative regulators of signal transducer and activator of transcription 5 (Stat5), including suppressor of cytokine signaling 1 (Socs1) and the protein tyrosine phosphatase Ptpn2. Expression of constitutively active Stat5a recapitulated the survival advantages conferred by miR-155, whereas constitutive Akt activation promoted sustained effector functions. Our results indicate that overexpression of miR-155 in tumorspecific T cells can be used to increase the effectiveness of adoptive immunotherapies in a cell-intrinsic manner without the need for life-threatening, lymphodepleting maneuvers.

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“…Moreover, the mir-155 family is a vital small regulatory RNA in organism, and the function is widely involved in immune adjustment (Vigorito et al, 2013) and a variety of cancers (MattiskeSuetani et al, 2012). Therefore, we constructed the target gene-pathway-cancer regulatory network of mir-155, and found CCND1, EGFR genes might be the key targets of mir-155 in cancer-related pathways.…”

Section: Discussionmentioning

confidence: 99%

Evolution of the Mir-155 Family and Possible Targets in Cancers and the Immune System

Xie

Liu²,

Pan³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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The mir-155 family is not only involved in a diversity of cancers, but also as a regulator of the immune system. However, the evolutionary history of this family is still unclear. The present study indicates that mir-155 evolved independently with lineage-specific gain of miRNAs. In addition, arm switching has occurred in the mir-155 family, and alternative splicing could produce two different lengths of ancestral sequences, implying the alternative splicing can also drive evolution for intragenic miRNAs. Here we screened validated target genes and immunityrelated proteins, followed by analyzation of the mir-155 family function by high-throughput methods like the gene ontology (GO) and Kyoto Eneyclopedin of Genes and Genemes (KEGG) pathway enrichment analysis. The high-throughput analysis showed that the CCND1 and EGFR genes were outstanding in being significantly enriched, and the target genes cebpb and VCAM1 and the protein SMAD2 were also vital in mir-155-related immune reponse activities. Therefore, we conclude that the mir-155 family is highly conserved in evolution, and CCND1 and EGFR genes might be potential targets of mir-155 with regard to progress of cancers, while the cebpb and VCAM1 genes and the protein SMAD2 might be key factors in the mir-155 regulated immune activities.

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miR‐155: an ancient regulator of the immune system

Cited by 265 publications

References 116 publications

Double-stranded microRNA mimics can induce length- and passenger strand–dependent effects in a cell type–specific manner

Double-stranded microRNA mimics can induce length- and passenger strand–dependent effects in a cell type–specific manner

miR-155 augments CD8 ⁺ T-cell antitumor activity in lymphoreplete hosts by enhancing responsiveness to homeostatic γ _c cytokines

Evolution of the Mir-155 Family and Possible Targets in Cancers and the Immune System

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miR‐155: an ancient regulator of the immune system

Cited by 265 publications

References 116 publications

Double-stranded microRNA mimics can induce length- and passenger strand–dependent effects in a cell type–specific manner

Double-stranded microRNA mimics can induce length- and passenger strand–dependent effects in a cell type–specific manner

miR-155 augments CD8 + T-cell antitumor activity in lymphoreplete hosts by enhancing responsiveness to homeostatic γ c cytokines

Evolution of the Mir-155 Family and Possible Targets in Cancers and the Immune System

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miR-155 augments CD8 ⁺ T-cell antitumor activity in lymphoreplete hosts by enhancing responsiveness to homeostatic γ _c cytokines