microRNAs targeting the immunomodulatory HLA-G gene: A new survey searching for microRNAs with potential to regulate HLA-G

Porto, Iane O. P.; Mendes-Junior, Celso Teixeira; Felício, Leandro Prado; Georg, Raphaela de Castro; Moreau, Philippe; Donadi, Eduardo Antônio; Chies, José Artur Bogo; Castelli, Erick C.

doi:10.1016/j.molimm.2015.01.030

Cited by 63 publications

(65 citation statements)

References 47 publications

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“…This close association between coding and regulatory region haplotypes was already observed for other non-classical HLA class I gene, such as HLA-G [51][52][53]. It should be noticed that even though a given HLA-E coding allele is associated with more stable mRNA or protein molecules, we should consider that the regulatory regions may influence expression levels by a myriad of mechanisms, including differential transcriptional factor binding [52] and differential microRNA binding [54]. The influence of the regulatory regions at the non classical HLA class I transcription levels has been explored and documented [reviewed at [52]].…”

Section: Tablesupporting

confidence: 63%

HLA-E coding and 3′ untranslated region variability determined by next-generation sequencing in two West-African population samples

et al. 2015

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Section: Tablesupporting

confidence: 63%

HLA-E coding and 3′ untranslated region variability determined by next-generation sequencing in two West-African population samples

et al. 2015

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“…Indeed, recent in silico searches for candidate microRNAs that could bind the HLA-G 3’UTR [43] have shown that the most relevant microRNAs modulating HLA-G expression do not target this region, whereas many potential target sites occur in the segment upstream of the +3165 position. Moreover, considering the seven HLA-G 3’UTR haplotypes evaluated here, the deleted sequence in 1Fter-4R constructions exhibits very limited polymorphism because the +3187 G, +3196 G and +3227 A variants are usually restricted to UTR-1, UTR-2 and UTR-18 respectively.…”

Section: Discussionmentioning

confidence: 99%

“…Among the mechanisms that could explain this observation, the 14-base sequence contains an AUUUG motif that might have an AU-pentamer–like effect on RNA decay [44]. Otherwise, in silico analyses have strongly suggested that the 14-base sequence could be a potential target site for microRNAs with the ability to regulate HLA-G expression [43]. Focusing on 3’UTR haplotypes, UTR-1 is classified as high plasma sHLA-G producer and is prone to a lower impact from endogenous factors in the present study.…”

Section: Discussionmentioning

confidence: 99%

“…From a mechanistic point of view, a panel of candidate microRNAs targeting UTR-1, UTR-2, UTR-3, UTR-4, UTR-5, UTR-6/-18 and UTR-7, the most frequent haplotypes has been recently inferred by using three independent algorithms: RNAhybrid, miRanda and PITA [43]. Although we are not aware that the predicted microRNAs actually exist within the cellular environment of each of the cell lines used here, some of these microRNAs could bind to non-polymorphic target sequences.…”

Section: Discussionmentioning

confidence: 99%

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Haplotypes of the HLA-G 3’ Untranslated Region Respond to Endogenous Factors of HLA-G+ and HLA-G- Cell Lines Differentially

et al. 2017

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The immune checkpoint HLA-G prevents maternal rejection of the fetus and contributes in cancer invasion and acceptance of allografts. The 5’ and 3’ regulatory regions of the HLA-G gene are polymorphic and balancing selection probably maintains this variability. It is proposed that nucleotide variations may affect the level of HLA-G expression. To investigate this issue we aimed to analyze how haplotypes of the 3’ untranslated region (3’UTR) with highest worldwide frequencies, namely UTR-1, UTR-2, UTR-3, UTR-4, UTR-5, UTR-18 and UTR-7, impact the expression of a luciferase reporter gene in vitro. Experiments performed with the HLA-G positive cell lines JEG-3 (choricarcinoma) and FON (melanoma), and with the HLA-G negative cell lines M8 (melanoma) and U251MG (glioblastoma) showed that the HLA-G 3’UTR polymorphism influences the response to endogenous cellular factors and may vary according to the cell type. UTR-5 and UTR-7 impact the activity of luciferase the most whereas UTR-2, UTR-3, UTR-4, and UTR-18 have intermediate impact, and UTR-1 has the lowest impact. These results corroborate the previous associations between amounts of plasma sHLA-G levels and 3’UTR haplotypes in healthy individuals and reinforce that 3’UTR typing may be a predictor of the genetic predisposition of an individual to express different levels of HLA-G.

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“…Regarding the HLA-G flanking regulatory regions, variation sites at the 5 0 URR may be key elements for regulation at transcriptional level, although the proper mechanisms are yet to be elucidated, since most of polymorphisms do not coincide with known regulatory elements. 30,36 On the other hand, both in silico 37,38 and in vitro [39][40][41] studies revealed that the genetic diversity at the 3 0 UTR do influence mRNA stability and translation. Signature of balancing selection has been disclosed at both flanking regulatory regions.…”

Section: The Hla-g Gene and Hla-g Moleculementioning

confidence: 99%

The role of HLA‐G in parasitic diseases

Sabbagh

Sonon

Sadissou

et al. 2018

HLA

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Little attention has been devoted to the role of HLA-G gene and molecule on parasitic disorders, and the available studies have focused on malaria, African and American trypanosomiasis, leishmaniosis, toxoplasmosis and echinococcosis. After reporting a brief description regarding the role of the cells of innate and adaptive immune system against parasites, we reviewed the major features of the HLA-G gene and molecule and the role of HLA-G on the major cells of immune system. Increased levels of soluble HLA-G (sHLA-G) have been observed in patients presenting toxoplasmosis and in the active phase of echinococcosis. In addition, increased sHLA-G has also been associated with increased susceptibility to malaria and increased susceptibility to develop human African trypanosomiasis (HAT). In contrast, decreased membrane-bound HLA-G has been reported in placenta of patients infected with Plasmodium falciparum and in heart and colon of patients presenting Chagas disease. The 3' untranslated region of the HLA-G gene has been the main focus of studies on malaria, HAT and Chagas disease, exhibiting distinct patterns of associations. Considering that HLA-G is an immune checkpoint molecule, inhibiting the activity of several cells of the immune system, the excessive neoexpression and the increased sHLA-G levels together with the decreased constitutive tissue expression of membrane-bound HLA-G may be detrimental to the host infected with parasite agents.

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microRNAs targeting the immunomodulatory HLA-G gene: A new survey searching for microRNAs with potential to regulate HLA-G

Cited by 63 publications

References 47 publications

HLA-E coding and 3′ untranslated region variability determined by next-generation sequencing in two West-African population samples

HLA-E coding and 3′ untranslated region variability determined by next-generation sequencing in two West-African population samples

Haplotypes of the HLA-G 3’ Untranslated Region Respond to Endogenous Factors of HLA-G+ and HLA-G- Cell Lines Differentially

The role of HLA‐G in parasitic diseases

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