Role of microRNAs and long non‑coding RNAs in glucocorticoid signaling (Review)

Abstract

The synthesis and release of glucocorticoids in living organisms are related to their response to unfavorable stressful conditions in order to maintain homeostatic functions and survive. One such hormone in humans is cortisol, which is produced by the hypothalamic‑pituitary‑adrenal cortex axis and binds with the glucocorticoid receptor (GR) following its secretion. GR controls a number of distinct gene networks. Non‑coding RNAs (ncRNAs), such as microRNAs (miRNAs) and long non‑coding RNAs (lncRNAs), regulate the expression and function of GR, having a considerable impact on various biological processes and treatment approaches for numerous disorders. In the present review, the GR pathways and signaling as part of the stress response system are discussed. A detailed report on the role of miRNAs and lncRNAs in glucocorticoid signaling is also presented.

Keywords: GR; endogenous glucocorticoids; glucocorticoid signaling; lncRNAs; miRNAs; stress response system.

Figure 1

Network of genes related to the NR3C1 gene. Association data include protein interactions (pink lines), pathways (light blue lines), co-expression (purple lines) and protein domain similarity (yellow lines). The network was constructed using the Genemania algorithm with the human network (44). NR3C1, nuclear receptor subfamily 3 group C member 1.

Figure 2

Circular diagram exhibiting the extended regulatory potential of microRNAs on the GRα network. A total of 120 microRNAs were predicted to target more than one transcript of the human NR3C1 network (constructed with Genemania). microRNA root thickness corresponds to the target prediction score, as generated by the miRDB algorithm. The diagram was built using R version 4.0.3 with the chorddiag (164) package. NR3C1, nuclear receptor subfamily 3 group C member 1; GR, glucocorticoid receptor.