NLRC5/CITA: A Key Player in Cancer Immune Surveillance

Yoshihama, Sayuri; Vijayan, Saptha; Sidiq, Tabasum; Kobayashi, Koichi S.

doi:10.1016/j.trecan.2016.12.003

Cited by 69 publications

(59 citation statements)

References 85 publications

(131 reference statements)

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“…FOXK1 has been determined to process the pivotal role in the etiology of many cancers [18]. There is an elevated expression of FOXK1 in breast cancer, and it could promote cell proliferation and migration [19].…”

Section: Discussionmentioning

confidence: 99%

WITHDRAWN: The LncRNA XIST Promotes Colorectal Cancer Cell Growth Through Regulating miR-497-5p/FOXK1 Axis

Wang

Jia

et al. 2020

Preprint

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Background: Recently, accumulated numbers of studies have reported that long noncoding RNAs (lncRNAs) process an important role in tumorigenesis. As a new member found in lncRNAs, the role of lncRNA XIST (XIST) in colorectal cancer (CRC) was still elusive. The objective of this study was conducted to characterize a novel regulatory network involving XIST in CRC cells. Methods: The mRNAs of XIST, miR-497-5p, and forkhead box k1 (FOXK1) in CRC cells and tissues were detected using quantitative real-time polymerase chain reaction (qRT-PCR). And the proliferation and apoptosis of CRC cells were determined using cell counting kit-8 assay and flow cytometry. Moreover, we also detected the cell migration and invasion using Transwell assays. The relationships between XIST, miR-497-5p, and FOXK1 were predicted and then the dual-luciferase reporter assay was used to their relationships. The protein level of FOXK1 was quantitated using western blot. Results: In CRC tissues and cell lines, XIST expression was up-regulated, in which also existed miR-497-5p down-regulation and FOXK1 up-regulation. XIST knockdown suppressed CRC cell proliferation and migration as well as its invasion. Moreover, blocking the XIST expression could inhibit CRC tumor growth in vivo and the effects were antagonized by loss of miR-497-5p. miR-497-5p was identified as a sponge of XIST and also targeted FOXK1 in CRC cells. Besides, XIST silencing-mediated inhibitory activity against CRC progression reversed miR-497-5p down-regulation or FOXK1 up-regulation. Conclusion: In conclusion, XIST promotes the malignancy of colon cancer cells partly by competitively binding to miR-497-5p, which then led to increased FOXK1 expression. We conclude that targeting XIST may be a possible treatment for colon cancer.

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Section: Discussionmentioning

confidence: 99%

WITHDRAWN: The LncRNA XIST Promotes Colorectal Cancer Cell Growth Through Regulating miR-497-5p/FOXK1 Axis

Wang

Jia

et al. 2020

Preprint

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“…One example that potentially contributes to the immunosuppressive phenotype found in G3 is the highly expressed mir-149, which has already been reported as dysregulated in many types of cancer including melanoma, where its upregulation influences the expression of both oncogenes and tumor suppressor genes [48]. In this study, we showed that the inhibition of its target, NLRC5, interferes with neo-antigen presentation, in agreement with other studies where it has been associated with immune evasion mechanisms and considered as a biomarker of immune surveillance [18].…”

Section: Discussionsupporting

confidence: 91%

“…It is well known that mutation and neoantigen burden are positively correlated to immunogenicity [17], however, although G2 and G3 show similar mutation and neoepitope burden and share the same mutational signature profile, they present different immunogenic profiles. Four different findings suggested immune evasion mechanisms in G3: [1] the stronger signature of checkpoint molecules which could induce T-cell exhaustion or compromise leukocyte activation and impair the supported anti-tumor immune response [46]; the suppression of antigen processing and presenting pathway, evidenced by [2] the higher dissociation constant (KD) of neoepitopes that diminishes antigen:HLA-I stability, which has been previously observed in other studies [47] and [3] the higher frequency of neoantigens in samples bearing mutations in the antigen processing and presenting pathway; [4] and downregulation of genes related to antigen presentation [17][18][19].…”

Section: Discussionmentioning

confidence: 77%

“…Although several mechanisms of immune evasion have been identified [17][18][19] and the effects of infiltrating immune cells on prognosis have been extensively reported for different tumor types [12,13], the immune microenvironment diversity and the reciprocal interplay between melanoma and non-tumoral host cells shaping the disease progression and patient's outcome is not fully understood. Therefore, the understanding of the specific contributions of each cell type to tumor growth can be a step toward developing new therapeutic strategies, predicting treatment resistance and avoiding selection of resistant populations.…”

mentioning

confidence: 99%

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Poor clinical outcome in metastatic melanoma is associated with a microRNA-modulated immunosuppressive tumor microenvironment

et al. 2020

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Background: Interaction between malignant cells and immune cells that reside within the tumor microenvironment (TME) modulate different aspects of tumor development and progression. Recent works showed the importance of miRNA-containing extracellular vesicles in this crosstalk. Methods: Interested in understanding the interplay between melanoma and immune-related TME cells, we characterized the TCGA's metastatic melanoma samples according to their tumor microenvironment profiles, HLA-I neoepitopes, transcriptome profile and classified them into three groups. Moreover, we combined our results with melanoma single-cell gene expression and public miRNA data to better characterize the regulatory network of circulating miRNAs and their targets related to immune evasion and microenvironment response. Results: The group associated with a worse prognosis showed phenotypic characteristics that favor immune evasion, including a strong signature of suppressor cells and less stable neoantigen:HLA-I complexes. Conversely, the group with better prognosis was marked by enrichment in lymphocyte and MHC signatures. By analyzing publicly available melanoma single-cell RNA and microvesicle microRNAs sequencing data we identified circulating micro-RNAs potentially involved in the crosstalk between tumor and TME cells. Candidate miRNA/target gene pairs with previously reported roles in tumor progression and immune escape mechanisms were further investigated and demonstrated to impact patient's overall survival not only in melanoma but across different tumor types. Conclusion: Our results underscore the impact of tumor-microenvironment interactions on disease outcomes and reveal potential non-invasive biomarkers of prognosis and treatment response.

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“…18,47 Additionally, NLRC5 is a critical player in maintaining immune surveillance. 16,48 For now, the biological function of IFIT5 remains elusive, recently one study found it was associated with epithelial to mesenchymal transition in renal cancer, but its potential role in immune regulation should be fully explored in tumors, especially in glioma. 49 Then we performed protein-protein interactions based on STRING database, 50 the results showed that IFIT5 may interact with some genes which exerts pivotal role in the IFN mediated signaling.…”

Section: Discussionmentioning

confidence: 99%

Development and validation of an interferon signature predicting prognosis and treatment response for glioblastoma

et al. 2019

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Background: Interferon treatment, as an important approach of anti-tumor immunotherapy, has been implemented in multiple clinical trials of glioma. However, only a small number of gliomas benefit from it. Therefore, it is necessary to investigate the clinical role of interferons and to establish robust biomarkers to facilitate its application. Materials and methods: This study reviewed 1,241 glioblastoma (GBM) and 1,068 lower grade glioma (LGG) patients from six glioma cohorts. The transcription matrix and clinical information were analyzed using R software, GraphPad Prism 7 and Medcalc, etc. Immunohistochemical (IHC) staining were performed for validation in protein level. Results: Interferon signaling was significantly enhanced in GBM. An interferon signature was developed based on five interferon genes with prognostic significance, which could reflect various interferon statuses. Survival analysis showed the signature could serve as an unfavorable prognostic factor independently. We also established a nomogram model integrating the risk signature into traditional prognostic factors, which increased the validity of survival prediction. Moreover, high-risk group conferred resistance to chemotherapy and high IFNB1 expression levels. Functional analysis showed that the high-risk group was associated with overloaded immune response. Microenvironment analysis and IHC staining found that high-risk group occupied a disorganized microenvironment which was characterized by an enrichment of M0 macrophages and neutrophils, but less infiltration of activated nature killing (NK) cells and M1 type macrophages. Conclusion: This interferon signature was an independent indicator for unfavorable prognosis and showed great potential for screening out patients who will benefit from chemotherapy and interferon treatment.

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NLRC5/CITA: A Key Player in Cancer Immune Surveillance

Cited by 69 publications

References 85 publications

WITHDRAWN: The LncRNA XIST Promotes Colorectal Cancer Cell Growth Through Regulating miR-497-5p/FOXK1 Axis

WITHDRAWN: The LncRNA XIST Promotes Colorectal Cancer Cell Growth Through Regulating miR-497-5p/FOXK1 Axis

Poor clinical outcome in metastatic melanoma is associated with a microRNA-modulated immunosuppressive tumor microenvironment

Development and validation of an interferon signature predicting prognosis and treatment response for glioblastoma

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