<i>miR‐155</i>expression in antitumor immunity: The higher the better?

Michaille, Jean‐Jacques; Awad, Hamdy; Fortman, Emily C; Efanov, Alexander A.; Tili, Esmerina

doi:10.1002/gcc.22698

Cited by 30 publications

(27 citation statements)

References 129 publications

(301 reference statements)

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“…These studies corroborate with our findings wherein miR-155 overexpressing GBM cells fail to induce prominent angiogenesis compared to control in chick CAM angiogenesis assay. Of late, it has been reported that miR-155 mediated gene regulation is dependent on the cellular context [52], and the phenotype associated with miR-155 targeting the same transcript in different cell types will probably be different [53]. However, the results from our study establish the tumor-suppressive role of miR-155 in AGTR1-positive subtype of GBM, wherein, its overexpression results in inhibition of multiple oncogenic properties and signaling pathways.…”

Section: Discussionmentioning

confidence: 53%

Targeting AGTR1/NF-κB /CXCR4 axis by miR-155 attenuates oncogenesis in Glioblastoma

Singh

Srivastava

Ateeq

2019

Preprint

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Glioblastoma (GBM) represents the most aggressive malignancy of the brain. Angiotensin II Receptor Type 1 (AGTR1) upregulation has been associated with proliferative and infiltrative properties of glioma cells. However, the underlying mechanism of AGTR1 upregulation in GBM is still unexplored. To understand the post-transcriptional regulation of AGTR1 in GBM, we screened 3'untranslated region (3'UTR) of AGTR1 by using prediction algorithms for binding of miRNA. Interestingly, miR-155 showed conserved binding on the 3'UTR of AGTR1, subsequently confirmed by AGTR1-3'UTR-luciferase reporter assay. Furthermore, stable miR-155 overexpressing GBM cells show decrease in AGTR1-mediated cell proliferation, invasion, foci formation and anchorage-independent growth. Strikingly, immunodeficient mice implanted with stable miR-155 overexpressing SNB19 cells show remarkable reduction (~95%) in tumor burden compared to control. Notably, miR-155 attenuates NF-κB signaling downstream of AGTR1 leading to reduced CXCR4 and AGTR1 levels. Mechanistically, miR-155 mitigates AGTR1-mediated, angiogenesis, epithelial-tomesenchymal transition, stemness, ERK/MAPK signaling and promotes apoptosis. Similar effects in cell-based assays were observed by using pharmacological inhibitor of IκB Kinase (IKK) complex. Taken together, we established that miRNA-155 post-transcriptionally regulates AGTR1 expression, abrogates AGTR1/NF-κB/CXCR4 signaling axis and elicits pleiotropic anticancer effects. This study opens new avenues for using IKK inhibitors and miRNA-155 replacement therapies for the treatment of AGTR1-positive malignancies.

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Section: Discussionmentioning

confidence: 53%

Targeting AGTR1/NF-κB /CXCR4 axis by miR-155 attenuates oncogenesis in Glioblastoma

Singh

Srivastava

Ateeq

2019

Preprint

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“…miR-155 targeting SHIP1 leads to the development of IFN-γ-producing CD4 + and CD8 + lymphocytes. Moreover, miR-155 in CD8 T cells decreases suppression of cytokine signaling 1 (SOCS1) activity, leading to an improved anticancer response, thus using both innate and adaptative immune cells [ 18 ]. Ji et al showed that miR-155 improves the antitumor response by epigenetically limiting CD8 + T cell differentiation and activity depletion [ 19 ].…”

Section: Resultsmentioning

confidence: 99%

“…miR-155 has a key role in preventing excessive immunosuppression through the control of PD-L1 levels, following TNF and IFN-γ stimulation [ 18 ]. PD-L1 is also the potential target gene of miR-142-5p.…”

Section: Resultsmentioning

confidence: 99%

“…Moreover, the expression of miR-155-5p is heavily repressed in tumors in advanced stages and in lymph node metastasis [ 15 ]. miR-155 regulates the production of INF-gamma, leading to a better anticancer response and preventing excessive immunosuppression [ 18 ]. Because most GC cases are diagnosed in advanced stages, Ma et al proposed a potential diagnostic biomarker function of miR-155 to detect the early stages of GC [ 16 ].…”

Section: Discussionmentioning

confidence: 99%

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Involvement of miR-142 and miR-155 in Non-Infectious Complications of CVID

et al. 2020

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Background and objectives: Common variable immunodeficiency (CVID) is the most prevalent antibody impairment. It is characterized by failure in immunoglobulin and protective antibody generation and defined by an increased tendency toward bacterial infections, autoimmunity, and malignancy. Most CVID diagnoses do not follow a classical Mendelian pattern of inheritance. In recent years, CVID has been considered an epigenetic phenomenon in the majority of cases, overtaking previous monogenetic and/or polygenetic theories. The aim of this study was to review the role of microRNAs (miRNAs) in CVID, focusing on the involvement of the same miRNAs in various non-infectious clinical complications of CVID, mainly autoimmunity and/or cancer. Materials and Methods: A bibliographic search of the scientific literature was carried out independently by two researchers in scientific databases and search engines. The MeSH terms “microRNAs” and “common variable immunodeficiency” were used. All research articles from inception to May 2020 were considered. Results: The literature data showed the involvement of two miRNAs in primary immunodeficiency: miR-142 and miR-155. Both of these miRNAs have been investigated through mice models, in which miR-142 and miR-155 were deleted. These knock-out (KO) mice models showed phenotypic analogies to CVID patients with hypogammaglobulinemia, adaptive immunodeficiency, polyclonal proliferation, lung disease, and enteric inflammation. miR-142 and miR-155 have been found to be involved in the following autoimmune and neoplastic clinical complications of CVID: Gastric cancer, gastric mucosa-associated lymphoid tissue (MALT) lymphoma, natural killer/Tcell lymphoma (NKTCL), and immune thrombocytopenia. Conclusions: miR-142 and miR-155 deregulation leads to similar CVID phenotypesin KO mice models. Although no data are available on the involvement of these miRNAs in human CVID, their dysregulation has been detected in human CVID comorbidities. The literature data show that miRNA sequences in murine models are comparable to those in humans; therefore, miR-142 and miR-155 involvement in human CVID could be hypothesized.

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“…Roles for miRNA were initially discovered in cancer biology and more recently, in physiological development and function, and in immunology . In particular, roles for miR‐155 in cancer and immunology have been demonstrated . Interestingly, the immunological role of miR‐155 can vary depending on the cell type.…”

Section: Introductionmentioning

confidence: 99%

Tissue‐specific production of MicroRNA‐155 inhibits melanocortin 5 receptor‐dependent suppressor macrophages to promote experimental autoimmune uveitis

et al. 2019

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Tissue-specific immune regulation is an important component of the immune response relevant to many areas of immunology. The focus of this study is on tissue-specific mechanisms that contribute to autoimmune uveitis. Precise gene regulation is necessary for the proper expression of an inflammatory or regulatory response. This precision gene regulation can be accomplished by microRNA at the level of the mRNA transcript. miR-155, in particular, has a complicated role in the immune response with positive and negative inflammatory effects. In this work, we identify a decrease in miR-155 in suppressor macrophages and further examine how tissue-specific production of miR-155 impacts experimental autoimmune uveitis. Importantly, we show that eliminating miR-155 expression by the target tissue before initiation reduces disease severity, but elimination of miR-155 after the onset of inflammation does not alter the course of disease. Additionally, expression of miR-155 by the target tissue before initiation is necessary for the induction of regulatory immunity that protects from further autoimmune disease, but not after the onset of inflammation. In summary, we find a MC5r-dependent decrease in miR-155 in postexperimental autoimmune uveitis APC, miR-155 production by the target tissue is necessary for the initiation of autoimmune uveitis, and may have a role in establishing protective regulatory immunity.Keywords: Autoimmunity r Experimental autoimmune uveitis r Macrophages r miR-155Additional supporting information may be found online in the Supporting Information section at the end of the article.

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miR‐155expression in antitumor immunity: The higher the better?

Cited by 30 publications

References 129 publications

Targeting AGTR1/NF-κB /CXCR4 axis by miR-155 attenuates oncogenesis in Glioblastoma

Targeting AGTR1/NF-κB /CXCR4 axis by miR-155 attenuates oncogenesis in Glioblastoma

Involvement of miR-142 and miR-155 in Non-Infectious Complications of CVID

Tissue‐specific production of MicroRNA‐155 inhibits melanocortin 5 receptor‐dependent suppressor macrophages to promote experimental autoimmune uveitis

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