In silico analysis of microRNAS targeting the HLA-G 3′ untranslated region alleles and haplotypes

Castelli, Erick C.; Moreau, Philippe; Chiromatzo, Alynne Oya e; Mendes-Junior, Celso Teixeira; Veiga‐Castelli, Luciana C.; Yaghi, Layale; Giuliatti, Silvana; Carosella, Edgardo D.; Donadi, Eduardo Antônio

doi:10.1016/j.humimm.2009.07.028

Cited by 143 publications

(130 citation statements)

References 25 publications

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“…As a consequence, NK cell-mediated cytotoxicity is increased. Further, it is predicted via in silico analysis that more miRNAs can bind to other SNPs in the 3'UTR, indicating that other miRNAs might be possible regulators of HLA-G as well (Castelli et al, 2009). These studies provide evidence that miRNAs can be important regulators of HLA-G gene expression in addition to the earlier described polymorphisms.…”

Section: Micrornasmentioning

confidence: 56%

“…An in silico screening of miRNAs that are potentially involved in the regulation of HLA-G revealed that miR19a had the exact same binding energy as miR-148a, miR-148b and miR-152 and also has a target site which included the +3142 polymorphism (Castelli et al, 2009). This indicates that miR-19a can have an important function in the regulation of HLA-G as well.…”

Section: Functional Consequences Of Hla-g Targeting By Micrornasmentioning

confidence: 95%

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How Micrornas Affect the Expression of Human Leukocyte Antigeng in Pregnancy

Kempers

Dijk

Oudejans

2012

American Journal of Immunology

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The expression of Human Leukocyte Antigen G (HLA-G) on Fetal Extravillous Trophoblast (EVT) cells during pregnancy plays an important role in preventing the fetus from rejection by suppressing the maternal immune system. Decreased expression levels of HLA-G have already shown to be associated with several complications of pregnancy such as pre-eclampsia. However, it remains largely unknown how HLA-G gene expression is regulated with regard to its function and its complications. Polymorphisms and microRNAs affect HLA-G gene expression and the formation of isoforms. Interestingly, three microRNAs, miR-148a, miR-148b and miR-152, downregulate HLA-G expression with functional consequences. Since HLA-G expression levels are reduced in pre-eclampsia without a known cause, we hypothesize that these microRNAs are involved in the development of pre-eclampsia. This review discusses how microRNAs can affect HLA-G gene expression and its functions. Additionally, the role of microRNAs in the development of pre-eclampsia will be reviewed.

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Section: Micrornasmentioning

confidence: 56%

Section: Functional Consequences Of Hla-g Targeting By Micrornasmentioning

confidence: 95%

How Micrornas Affect the Expression of Human Leukocyte Antigeng in Pregnancy

Kempers

Dijk

Oudejans

2012

American Journal of Immunology

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“…This region contains several regulatory elements (Kuersten and Goodwin, 2003), including polyadenylation signals, AU-rich elements (Alvarez et al, 2009), and several polymorphic sites that may potentially influence mRNA stability, turnover, mobility and splicing pattern. 3'UTR polymorphisms that can influence HLA-G expression are: i) the insertion (INS) or deletion (DEL) of a 14bp fragment (14bp INS/DEL) that has been associated with mRNA stability; ii) the SNP at position +3142, which may be a target for certain microRNAs (miRNAs), small RNA sequences which once bound to a complementary mRNA lead to its translational repression or degradation and gene silencing (Bartel, 2009); iii) additional six SNPs landed in putative binding sites for miRNAs (Castelli et al, 2009) (Fig.4).…”

Section: 'Untraslated Region (Utr)mentioning

confidence: 99%

“…Notably, the presence of 14bp DEL has been found to be predictive for the incidence of GvHD after unrelated (La Nasa et al, 2007) and HLA-identical sibling (Sizzano et al, in press) Human Stem Cell Transplantation (HSCT) for beta-thalassemia. Several SNPs at 3'UTR of HLA-G locus have been identified (Castelli et al, 2009). Among them, the +3142 C/G SNP has been proposed to be critically involved in HLA-G regulation since it is associated with asthma (Tan et al, 2005).…”

Section: 'Untraslated Region (Utr)mentioning

confidence: 99%

“…In silico analysis of the 3'UTR of the HLA-G locus revealed the presence of additional six SNPs that are landed in putative binding sites for miRNAs (Castelli et al, 2009). Interestingly the 14bp INS/DEL and the 7 SNPs arrange in different combinations to generate eight distinct haplotypes of 3'UTR HLA-G region (Castelli et al, 2010) (Table 1).…”

Section: 'Untraslated Region (Utr)mentioning

confidence: 99%

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Distinctive Immunological Functions of HLA-G

Amodio¹,

Gregori²

2012

Histocompatibility

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HLA‐G expression is associated with metastasis and poor survival in the Balb/c nu/nu murine tumor model with ovarian cancer

Lin¹,

Zhang²,

Xu³

et al. 2011

Intl Journal of Cancer

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Aberrant HLA-G expression is associated with tumor invasiveness and poor clinical prognosis; however, there is a lack of preclinical animal model to address whether HLA-G plays a causal role in the unfavorable prognosis of malignancies. In the current study, ovarian carcinoma cell lines (HO-8910 and Ovcar-3) were transfected with HLA-G gene. HLA-G expression was analyzed with western blot and flow cytometry. Transwell experiment was performed to analyze the cell migration and invasion capability and/or multicellular spheroid formation was investigated with the 3D culture assay in vitro. The effects of HLA-G expression for tumor cell organ metastasis and for mouse survival was analyzed with the Balb/c nu/nu mouse model. Our data showed that HO-8910-G and Ovcar-3-G cells are of higher invasion potential compared with the parental HO-8910 and Ovcar-3 cells. Multicellular spheroid formation exists only in HO-8910-G cells in a 3D culture assay. In Balb/c nu/nu mouse model, widespread metastasis was observed in mice xenografted with HO-8910-G cells, but not in the group with parental cells. Mouse survival was dramatically decreased in HO-8910-G and Ovcar-3-G xenografted mice than that with HO-8910 and Ovcar-3 cells, respectively. In summary, our study provided the first evidence that HLA-G expression is associated with tumor metastasis and with poor survival in an animal model with ovarian cancer.

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In silico analysis of microRNAS targeting the HLA-G 3′ untranslated region alleles and haplotypes

Cited by 143 publications

References 25 publications

How Micrornas Affect the Expression of Human Leukocyte Antigeng in Pregnancy

How Micrornas Affect the Expression of Human Leukocyte Antigeng in Pregnancy

Distinctive Immunological Functions of HLA-G

HLA‐G expression is associated with metastasis and poor survival in the Balb/c nu/nu murine tumor model with ovarian cancer

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