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Regulation of the Human Fc-Neonatal Receptor alpha-Chain Gene FCGRT by MicroRNA-3181

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Abstract

Purpose

FCGRT encodes the alpha-chain component of the neonatal Fc receptor (FcRn). FcRn is critical for the trafficking of endogenous and exogenous IgG molecules and albumin in various tissues. Few regulators of FcRn expression have been identified. We investigated the epigenetic regulation of FcRn by two microRNAs (hsa-miR-3181 and hsa-miR-3136-3p) acting on FCGRT.

Methods

The binding of candidate microRNAs to the 3′-untranslated region of FCGRT was evaluated using luciferase reporter constructs in CHO cells. The effect of microRNAs on FCGRT mRNA and FcRn protein expression was evaluated using specific microRNA mimics and inhibitor transfections in A549, HEK293 and HepG2 cells.

Results

Hsa-miR-3181 mimic reduced luciferase reporter activity by 70.1% (10 nM, P < 0.0001). In A549, HEK293 and HepG2 cells, hsa-miR-3181 decreased FCGRT mRNA expression (48.6%, 51.3% and 43.5% respectively, 25 nM, P < 0.05). The hsa-miR-3181 mimic decreased the expression of FcRn protein by 40% after 48 h (25 nM, P < 0.001). The mature form of hsa-miR-3181 was detected in samples of human liver.

Conclusions

These data suggest that hsa-miR-3181 is an epigenetic regulator of FCGRT expression. The identification of this regulator of FCGRT may provide insights into a potential determinant of interindividual variability in FcRn expression.

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Abbreviations

3’UTR:

3-prime untranslated region

FCGRT :

Fc-neonatal receptor gene

FcRn:

Fc-neonatal Receptor

IVIG:

Intravenous immunoglobulin

microRNA-3136-3p:

Hsa-miR-3136-3p

microRNA-3181:

Hsa-miR-3181

VNTR:

Variable number tandem repeat

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Acknowledgments and Disclosures

This study was supported by the Eugene Kennedy Shriver National Institute of Child Health and Human Development (award HD089053) and the National Institute of General Medical Sciences (award GM073646).

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, The State University of New York, 470 Kapoor Hall, Buffalo, New York, 14214, USA

    Daniel C. Ferguson & Javier G. Blanco

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  1. Daniel C. Ferguson
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  2. Javier G. Blanco
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Correspondence to Javier G. Blanco.

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Ferguson, D.C., Blanco, J.G. Regulation of the Human Fc-Neonatal Receptor alpha-Chain Gene FCGRT by MicroRNA-3181. Pharm Res 35, 15 (2018). https://doi.org/10.1007/s11095-017-2294-0

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