Differential Expression of Genes Related to Calcineurin and MTOR Signaling and Regulatory MiRNAs in Peripheral Blood from Kidney Recipients Under Tacrolimus-based Therapy

Overview

Journal Ann Transl Med

Publisher AME Publishing Company

Date 2020 Nov 4

PMID 33145270

Citations 5

Authors

Vivian Bonezi

Fabiana Dalla Vecchia Genvigir

Patricia de Cassia Salgado

Claudia Rosso Felipe

Helio Tedesco-Silva Jr

Jose Osmar Medina-Pestana

Alvaro Cerda

Sonia Quateli Doi

Mario Hiroyuki Hirata

Rosario Dominguez Crespo Hirata

Affiliations

Soon will be listed here.

Abstract

Background: Genetic and epigenetics factors have been implicated in drug response, graft function and rejection in solid organ transplantation. Differential expression of genes involved in calcineurin and mTOR signaling pathway and regulatory miRNAs was analyzed in the peripheral blood of kidney recipient cohort (n=36) under tacrolimus-based therapy.

Methods: , , , , and mRNA expression and polymorphisms in and were analyzed by qPCR. Expression of miRNAs targeting (miR-30a, miR-145), (miR-10b), (miR-99a, miR-100), and (miR-103a) was measured by qPCR array.

Results: and mRNA levels were reduced in the first three months of treatment compared to pre-transplant (P<0.05). , , , and expression was not changed. In the 3 month of treatment, the expression of miR-99a, which targets , increased compared to pre-transplant (P<0.05). c.249G>A (GG genotype) and c.2997C>T (TT genotype) were associated with reduced expression of mRNA and , respectively. mRNA levels were higher in patients with acute rejection (P=0.026).

Conclusions: The expression of and miR-99a in the peripheral blood of renal recipients is influenced by tacrolimus-based therapy and by and variants. These molecules can be potential biomarkers for pharmacotherapy monitoring.

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