TLR4 Polymorphisms and Expression in Solid Cancers

Pandey, Nilesh; Chauhan, Alex; Jain, Neeraj

doi:10.1007/s40291-018-0361-9

Cited by 28 publications

(22 citation statements)

References 181 publications

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“…Furthermore, we observed the 3′ UTR heterozygous genotype GC of TLR4 rs11536889 to be associated with increased risk of cervical cancer in our study subjects. A similar observation was found in bladder cancer 50 , however, the association status of this SNP with other cancers was inconsistent 32 . Moreover, the G allele of TLR4 rs11536889 3′ UTR SNP has been suggested to play a key role in inhibiting TLR4 translation in monocytes 51 .…”

Section: Discussionsupporting

confidence: 60%

“…Reports on the influence of TLR4 and TLR9 single nucleotide polymorphisms (SNPs) in cervical cancer susceptibility are limited as well as conflicting 30–32 . In the case of TLR4 polymorphisms, Asp299Gly (rs4986790) and Thr399Ile (rs4986791) were shown to be associated with tumor progression, however, no direct association of these SNPs was found in case-control set up 33,34 .…”

Section: Introductionmentioning

confidence: 99%

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Association of TLR4 and TLR9 polymorphisms and haplotypes with cervical cancer susceptibility

Pandey

Chauhan

Raithatha

et al. 2019

Sci Rep

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single nucleotide polymorphisms (sNps) in TLR genes may serve as a crucial marker for early susceptibility of various cancers including cervical cancer. the present study was therefore designed to ascertain the role of TLR4 and TLR9 sNps and haplotypes to hrHpV infection and cervical cancer susceptibility. The study included 110 cervical cancer biopsies and 141 cervical smears from age-matched healthy controls of Gujarati ethnicity of Western India. hrHPV 16 and 18 were detected using Realtime pCR. eight sNps, four each in TLR4 and TLR9 were analyzed using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism and Allele-Specific PCR. HPV 16 and 18 were detected in 68% cervical cancer cases. TLR4 rs4986790, rs1927911 and TLR9 rs187084 showed association with HPV 16/18 infection. CC and CT genotypes of TLR4 rs11536889 and rs1927911 respectively, and TC, CC genotypes of TLR9 rs187084, as well as minor alleles of TLR4 rs4986790 and TLR9 rs187084, were associated with the increased risk of cervical cancer. Stage-wise analysis revealed TLR9 rs187084 and rs352140 to be associated with early-stage cancer. TLR4 haplotype GtAC and TLR9 haplotype GATC were associated with the increased risk of cervical cancer while TLR4 haplotype GCAG was associated with the decreased risk. TLR4 haplotype GCAG and TLR9 haplotype GAtC showed association with increased susceptibility to hrHpV infection. In conclusion, the present study revealed association of TLR4 and TLR9 polymorphisms and haplotypes with hrHpV infection and cervical cancer risk. Further evaluation of a larger sample size covering diverse ethnic populations globally is warranted. With respect to gender-specific cancers, cervical cancer is the next major cause of global cancer deaths among women, after the cancer of the breast, wherein India accounts for almost one-fourth of total cervical cancer-related mortalities 1. Human papillomavirus (HPV) infection is considered as the most vital event in the development and progression of cervical cancer, as the HPV DNA has been detected in almost all of the cervical tumors globally 2. With more than 200 HPV types known till date,

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Section: Discussionsupporting

confidence: 60%

Section: Introductionmentioning

confidence: 99%

Association of TLR4 and TLR9 polymorphisms and haplotypes with cervical cancer susceptibility

Pandey

Chauhan

Raithatha

et al. 2019

Sci Rep

View full text Add to dashboard Cite

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“…The immune-reactive bands were quantified by densitometry using Image So far, studies of CRC research have mostly focused on TLR4. Increased TLR4 expression correlates with advanced CRC stage and decreased survival in CRC patients [23,24]. Fukada and coworkers reported that TLR4 is also upregulated in inflammation-associated CRC in both humans and in experimental models [25].…”

Section: Discussionmentioning

confidence: 99%

Selective targeting of the TLR4 co-receptor, MD2, prevents colon cancer growth and lung metastasis

Rajamanickam¹,

Yan²,

Xu³

et al. 2020

Int. J. Biol. Sci.

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Toll-like receptor (TLR) signaling is an emerging pathway in tumor cell invasion and metastasis. Myeloid differentiation protein-2 (MD2) contributes to ligand recognition and activation of TLRs in response to exogenous microbial insults or endogenous agents. We hypothesized that blocking MD2 using a specific inhibitor would prevent TLR4-mediated inflammatory responses and metastatic cancer growth. Here, we report that a MD2 inhibitor, L6H21, inhibited migration and invasion of LPS-activated colon cancer CT26.WT cells. These activities were accompanied by inhibition of nuclear factor-κB (NF-κB) activation, and thereby inhibition of the production of pro-inflammatory cytokines and adhesive molecules in colon cancer cells. Furthermore, L6H21 inhibited CT26.WT metastasis to the lung in BALB/c mice as well as suppressed colitis-induced colon cancer induced by azoxymethane/dextran sulfate sodium (AOM/DSS). Taken together, our results demonstrated that L6H21 suppressed tumor invasion and metastasis through blocking TLR4-MD2/NF-κB signaling axis. These findings reveal that inhibition of MD2 may be an important target for the development of colon cancer therapies.

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“…Among the genes with novel recurrent mutations, TLR4 (Toll‐like receptor 4) primarily functions as a pathogen‐associated molecular pattern recognition receptor (i.e., bacterial LPS) in the innate immune system. Additionally, TLR4 is overexpressed in different cancer types, and several tumor ligands that stimulate TLR4 signaling through NF‐κB have been described (Pandey, Chauhan, & Jain, ). Here, we identified a recurrent mutation in the 3’UTR of TLR4 , which might affect the post‐transcriptional modulation of TLR4 via miRNA.…”

Section: Discussionmentioning

confidence: 99%

Functional analysis of RPS27 mutations and expression in melanoma

Floristán

Morales

Hanniford

et al. 2019

Pigment Cell Melanoma Res

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Next‐generation sequencing has enabled genetic and genomic characterization of melanoma to an unprecedent depth. However, the high mutational background plus the limited depth of coverage of whole‐genome sequencing performed on cutaneous melanoma samples make the identification of novel driver mutations difficult. We sought to explore the somatic mutation portfolio in exonic and gene regulatory regions in human melanoma samples, for which we performed targeted sequencing of tumors and matched germline DNA samples from 89 melanoma patients, identifying known and novel recurrent mutations. Two recurrent mutations found in the RPS27 promoter associated with decreased RPS27 mRNA levels in vitro. Data mining and IHC analyses revealed a bimodal pattern of RPS27 expression in melanoma, with RPS27‐low patients displaying worse prognosis. In vitro characterization of RPS27‐high and RPS27‐low melanoma cell lines, as well as loss‐of‐function experiments, demonstrated that high RPS27 status provides increased proliferative and invasive capacities, while low RPS27 confers survival advantage in low attachment and resistance to therapy. Additionally, we demonstrate that 10 other cancer types harbor bimodal RPS27 expression, and in those, similarly to melanoma, RPS27‐low expression associates with worse clinical outcomes. RPS27 promoter mutation could thus represent a mechanism of gene expression modulation in melanoma patients, which may have prognostic and predictive implications.

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TLR4 Polymorphisms and Expression in Solid Cancers

Cited by 28 publications

References 181 publications

Association of TLR4 and TLR9 polymorphisms and haplotypes with cervical cancer susceptibility

Association of TLR4 and TLR9 polymorphisms and haplotypes with cervical cancer susceptibility

Selective targeting of the TLR4 co-receptor, MD2, prevents colon cancer growth and lung metastasis

Functional analysis of RPS27 mutations and expression in melanoma

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