LYAR promotes colorectal cancer cell mobility by activating galectin-1 expression

Wu, Yupeng; Liu, Ming; Li, Zhuchen; Wu, Xiaobin; Wang, Ying; Wang, Yadong; Nie, Min; Huang, Feifei; Ju, Junyi; Ma, Chi; Tan, Renxiang; Zen, Ke; Zhang, Chenyu; Ke-qin, FU; Chen, Yugen; Wang, Ming-Rong; Zhao, Quan

doi:10.18632/oncotarget.5335

Cited by 22 publications

(25 citation statements)

References 29 publications

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“…For C06 in particular, the top five differentially expressed (DE) genes (ranked on p-value) were CCL5, GZMK, CXCR3, LYAR, and NKG7 ( Supplementary Table S2), as shown in the UMAP plots colored by relative expression ( Figure 2C). CXCR3, CCL5, and NKG7 have all been associated previously with T H 1 migratory capacity (55,56) and phenotype (57), while the expression of GZMK and LYAR likely indicate a cytotoxic and activated population (58,59). Figure 2C also depicts the canonical Treg markers, FOXP3 and IKZF2, which were highly expressed in the majority of APB and CB Treg clusters but only lowly expressed in C06.…”

Section: Scrna-seq Identifies Contaminants In Pre-expanded Tregsmentioning

confidence: 59%

Human Regulatory T Cells From Umbilical Cord Blood Display Increased Repertoire Diversity and Lineage Stability Relative to Adult Peripheral Blood

et al. 2020

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Tregs. Interestingly, expression of canonical Treg markers, such as FOXP3, TIGIT, and IKZF2, were increased in CB CD4 + CD127 + conventional T cells (Tconv) compared to APB Tconv, post-expansion, implying perinatal T cells may adopt a default regulatory program. Collectively, these data identify surface markers (namely CXCR3) that could be depleted to improve purity and stability of APB Tregs, and support the use of expanded CB Tregs as a potentially optimal ACT modality for the treatment of autoimmune and inflammatory diseases.

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Section: Scrna-seq Identifies Contaminants In Pre-expanded Tregsmentioning

confidence: 59%

Human Regulatory T Cells From Umbilical Cord Blood Display Increased Repertoire Diversity and Lineage Stability Relative to Adult Peripheral Blood

et al. 2020

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“…On the other hand, the expression of NF-B-regulated proinflammatory cytokines, including IL-6, IL-8, IL-1␤, and TNF-␣ are also inhibited by LYAR, and LYAR inhibits the NF-B promoter activity, suggesting that LYAR may participate in the NF-B signaling pathway, thus regulating cellular inflammatory responses, and further investigations would benefit for a comprehensive understanding of LYAR's role in innate immunity. LYAR is a transcription factor, and two zinc finger DNA binding motifs in its N-terminal domain are regarded to be involved in transcriptional regulation (26,31,32). This raises the concern that the inhibitory activity of LYAR in antiviral gene expression might be an effect of its transcriptional repression of those genes.…”

Section: Discussionmentioning

confidence: 99%

LYAR Suppresses Beta Interferon Induction by Targeting Phosphorylated Interferon Regulatory Factor 3

Yang

Liu

Cheng

et al. 2019

J Virol

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The innate immune response is vital for host defense and must be tightly controlled, but the mechanisms responsible for its negative regulation are not fully understood. The cell growth-regulating nucleolar protein LYAR was found to promote replication of multiple viruses in our previous study. Here, we report that LYAR acts as a negative regulator of innate immune responses. We found that LYAR expression is induced by beta interferon (IFN-β) during virus infection. Further studies showed that LYAR interacts with phosphorylated IFN regulatory factor 3 (IRF3) to impede the DNA binding capacity of IRF3, thereby suppressing the transcription of IFN-β and downstream IFN-stimulated genes (ISGs). In addition, LYAR inhibits nuclear factor-κB (NF-κB)-mediated expression of proinflammatory cytokines. In summary, our study reveals the mechanism of LYAR in modulating IFN-β-mediated innate immune responses by targeting phosphorylated IRF3, which not only helps us to better understand the mechanisms of LYAR-regulated virus replication but also uncovers a novel role of LYAR in host innate immunity. IMPORTANCE Type I interferon (IFN-I) plays a critical role in the antiviral innate immune responses that protect the host against virus infection. The negative regulators of IFN-I are important not only for fine-tuning the antiviral responses to pathogens but also for preventing excessive inflammation. Identification of negative regulators and study of their modulation in innate immune responses will lead to new strategies for the control of both viral and inflammatory diseases. Here, we report for the first time that the cell growth-regulating nucleolar protein LYAR behaves as a repressor of host innate immune responses. We demonstrate that LYAR negatively regulates IFN-β-mediated immune responses by inhibiting the DNA binding ability of IFN regulatory factor 3 (IRF3). Our study reveals a common mechanism of LYAR in promoting different virus replication events and improves our knowledge of host negative regulation of innate immune responses.

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“…GPR64 is known to be involved in the adhesion and migration of breast cancer cells through mechanisms including a noncanonical NFkB pathway . Furthermore, it was reported that transcription factor LYAR promote tumor cell migration and invasion by upregulating galectin‐1 gene expression in colorectal cancer . Another interesting network link was RFC5 (activated by TRPS1 in B42‐11 and B42‐16) as it appeared in many (10 out of 14) pathways related to DNA repair and cell cycle/mitosis from the differential expression analysis and is among the top five genes correlating with TRPS1.…”

Section: Discussionmentioning

confidence: 99%

“…39 Furthermore, it was reported that transcription factor LYAR promote tumor cell migration and invasion by upregulating galectin-1 gene expression in colorectal cancer. 40 Another interesting network link was RFC5 (activated by TRPS1 in B42-11 and B42-16) as it appeared in many (10 out of 14) pathways related to DNA repair and cell cycle/mitosis from the differential expression analysis and is among the top five genes correlating with TRPS1. The RFC5 gene belongs to the replication factor C family and was described to reflect the hallmark of cancer "genomic instability."…”

Section: Discussionmentioning

confidence: 99%

Expression of miRNA‐26b‐5p and its target TRPS1 is associated with radiation exposure in post‐Chernobyl breast cancer

Wilke

Heß

Klymenko

et al. 2017

Intl Journal of Cancer

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Ionizing radiation is a well-recognized risk factor for the development of breast cancer. However, it is unknown whether radiation-specific molecular oncogenic mechanisms exist. We investigated post-Chernobyl breast cancers from radiation-exposed female clean-up workers and nonexposed controls for molecular changes. Radiation-associated alterations identified in the discovery cohort (n = 38) were subsequently validated in a second cohort (n = 39). Increased expression of hsa-miR-26b-5p was associated with radiation exposure in both of the cohorts. Moreover, downregulation of the TRPS1 protein, which is a transcriptional target of hsa-miR-26b-5p, was associated with radiation exposure. As TRPS1 overexpression is common in sporadic breast cancer, its observed downregulation in radiation-associated breast cancer warrants clarification of the specific functional role of TRPS1 in the radiation context. For this purpose, the impact of TRPS1 on the transcriptome was characterized in two radiation-transformed breast cell culture models after siRNA-knockdown. Deregulated genes upon TRPS1 knockdown were associated with DNA-repair, cell cycle, mitosis, cell migration, angiogenesis and EMT pathways. Furthermore, we identified the interaction partners of TRPS1 from the transcriptomic correlation networks derived from gene expression data on radiation-transformed breast cell culture models and sporadic breast cancer tissues provided by the TCGA database. The genes correlating with TRPS1 in the radiation-transformed breast cell lines were primarily linked to DNA damage response and chromosome segregation, while the transcriptional interaction partners in the sporadic breast cancers were mostly associated with apoptosis. Thus, upregulation of hsa-miR-26b-5p and downregulation of TRPS1 in radiation-associated breast cancer tissue samples suggests these molecules representing radiation markers in breast cancer.

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LYAR promotes colorectal cancer cell mobility by activating galectin-1 expression

Cited by 22 publications

References 29 publications

Human Regulatory T Cells From Umbilical Cord Blood Display Increased Repertoire Diversity and Lineage Stability Relative to Adult Peripheral Blood

Human Regulatory T Cells From Umbilical Cord Blood Display Increased Repertoire Diversity and Lineage Stability Relative to Adult Peripheral Blood

LYAR Suppresses Beta Interferon Induction by Targeting Phosphorylated Interferon Regulatory Factor 3

Expression of miRNA‐26b‐5p and its target TRPS1 is associated with radiation exposure in post‐Chernobyl breast cancer

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