Toll-like receptor 3 acts as a suppressor gene in breast cancer initiation and progression: a two-stage association study and functional investigation

Fan, Lei; Zhou, Peng; Hong, Quan; Chen, Ao-Xiang; Li, Guangyu; Yu, Ke-Da; Shao, Zhi‐Ming

doi:10.1080/2162402x.2019.1593801

Cited by 21 publications

(24 citation statements)

References 53 publications

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“…Several of TLR agonists have been investigated in clinical studies for their potential function in antitumor immunity (2)(3)(4). Toll-like receptor 3 (TLR3), as one of important TLR members, is participated in the development of many tumors by recognizing and binding to its corresponding ligands (5)(6)(7)(8)(9). TLR3 has been reported to express on normal epithelial cells, such as lung tissue.…”

Section: Introductionmentioning

confidence: 99%

Methylation Regulation of TLR3 on Immune Parameters in Lung Adenocarcinoma

Tian

et al. 2021

Front. Oncol.

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This study aims to analyze the methylation regulation of TLR3 in lung adenocarcinoma (LUAD) and to explore the association of TLR3 expression with immune microenvironment. TLR3 has a decreased expression in LUAD tissues and low expression of TLR3 is not only associated with poor prognosis in patients with LUAD, but also can be used as a diagnostic marker. Bisulfite sequencing PCR (BSP) results showed that the methylation level in the promoter of TLR3 was negatively correlated with the level of TLR3 mRNA in LUAD tissues. TIMER analysis showed that TLR3 was negatively correlated with the tumor purity of LUAD and positively with immune cell infiltration to some extent. ESTIMATE analysis also suggested that TLR3 expression and its methylation had significant correlation with immune score. The lower immune scores were associated with the late stage of LUAD and poor prognosis. The high expression of TLR3 might inhibit the development of LUAD by activating apoptosis pathway. The proteins interacted with TLR3 were mainly involved in the apoptosis pathway and positively correlated with the key genes (MYD88, Caspase 8, BIRC3, PIK3R1) in this pathway. Therefore, TLR3 as a key biomarker for prognosis and diagnosis in LUAD, might be considered as a potential epigenetic and immunotherapeutic target.

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Section: Introductionmentioning

confidence: 99%

Methylation Regulation of TLR3 on Immune Parameters in Lung Adenocarcinoma

Tian

et al. 2021

Front. Oncol.

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“…We found that the T-allele of rs5743312 and the T-allele of rs3775296 conferred an increased risk of breast cancer incidence. 9 Chen et al reported that the SNP rs3775291 in TLR3 may influence breast cancer patient outcome. 2 However, Etokebe et al reported that polymorphisms in the TLR3 gene were not likely to be associated with an increased risk for developing breast cancer.…”

Section: Discussionmentioning

confidence: 99%

“…7,8 In our previous study, we found that common genetic changes in the TLR3 gene may influence breast cancer susceptibility and development. 9 TLR3 plays a negative regulatory role in the initiation and progression of human breast cancer cells, at least in part by downregulating the EGFR/ PI3K/AKT pathway. 9 However, all the single nucleotide polymorphisms (SNPs) in our previous study were only markers of the TLR3 gene, not causative polymorphisms.…”

Section: Introductionmentioning

confidence: 99%

Toll-like receptor 3 -926T>A increased the risk of breast cancer through decreased transcriptional activity

Fan

Zhou²,

Chen

et al. 2019

OncoImmunology

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Toll-like receptor 3 (TLR3) is a viral sensor that induces apoptosis in response to double-stranded RNA (dsRNA). Common genetic changes in the TLR3 gene may influence breast cancer susceptibility and development. However, all of the polymorphisms in the previous study were only markers of the TLR3 gene, not causative polymorphisms. In this study, we performed a case-control study focusing on the relationship between rs5743305 (−926T>A), a single nucleotide polymorphism (SNP) in the promoter region of TLR3, and breast cancer. We found that the genetic variant rs5743305 increased the risk of breast cancer under the dominant and codominant models (dominant model:

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“…Four SNPs located in the genes TLR3 (rs3775291, rs3775294, rs5743305) and TLR7 (rs3853839) were selected from the International HapMap project (International HapMap, 2003) and according to their association with the susceptibility to autoimmune diseases and for their potential functional relevance (Deng et al, 2013;Fan, Zhou, Hong, et al, 2019;Ranjith-Kumar et al, 2007). Thus, SNPs that could influence gene expression through changes in promoter activity, the stability of messenger RNA, protein functioning and/or pathogenic clinical significance.…”

Section: Snps Selection and Genotypingmentioning

confidence: 99%

RNA receptors, TLR3 and TLR7, are potentially associated with SLE clinical features

Elloumi

Fakhfakh

Abida

et al. 2021

Int J Immunogenetics

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The influence of intracellular Toll-like-receptors (TLR), recognized as nucleic acid sensors, in the immunopathogenesis of systemic lupus erythematosus (SLE) is increasingly explored. Yet, the results of both functional and genetic studies remain conflictual. We evaluated the association between TLR3 and TLR7 genes selected variants and SLE and investigated the possible relationship with clinical and serological parameters. Then, we studied the genetic expression of these receptors, and if the TLR7 gene evades X chromosome inactivation (XCI). Our study covers 106 cases and 200 controls, genotyped using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. TLR3 and TLR7 expression level was assessed by qPCR carried, respectively, on renal tissues and PBMC, and methylation status was evaluated by methylation-specific PCR. Results were statistically analysed using SheSiS software, χ 2 , and Mann-Whitney test. Significant associations with SLE susceptibility were found for the TLR3 rs3775291, rs5743305 and rs3775294 polymorphisms. Further subgroup analysis, TLR3 rs3775291 and rs3775294 polymorphisms were significantly associated with lupus nephritis (LN) and even correlate with the presence of auto-antibodies binding RNA molecules. SLE and LN were more common in men with rs3853839-G variant within TLR7 gene versus those carrying the C allele. Moreover, the role of the G allele in the TLR7 expression up-regulation was confirmed. However, gene expression analysis showed no significant differences in TLR3 and TLR7 mRNA levels between LN patient biopsies and healthy tissues (p > .05). When comparing patients and controls, no statistical difference was observed in XCI pattern. Otherwise, notable associations were raised between TLR3 and TLR7 gene variants and clinical and serological lupus features pointing towards the role of genetic background in the physiopathogenesis of the disease.

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Toll-like receptor 3 acts as a suppressor gene in breast cancer initiation and progression: a two-stage association study and functional investigation

Cited by 21 publications

References 53 publications

Methylation Regulation of TLR3 on Immune Parameters in Lung Adenocarcinoma

Methylation Regulation of TLR3 on Immune Parameters in Lung Adenocarcinoma

Toll-like receptor 3 -926T>A increased the risk of breast cancer through decreased transcriptional activity

RNA receptors, TLR3 and TLR7, are potentially associated with SLE clinical features

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