MicroRNA-181a-5p enhances cell proliferation in medullary thymic epithelial cells via regulating TGF-β signaling

Abstract

The expression profiles of miRNAs in thymus tissues from mice of different age have been demonstrated in our previous study. After an integrated analysis of the miRNA expression profiles, we demonstrated that the expression of miR-181a-5p was significantly decreased in thymic epithelial cells (TECs) from 10-to 19-month-old mice when compared with that in TECs from 1-month-old mice by quantitative reverse transcriptase polymerase chain reaction. We hypothesized that miR-181a-5p in TECs might be associated with the age-related thymus involution through regulating some genes or signaling pathway. To test this hypothesis, the mouse medullary thymic epithelial cells (MTEC1) were used. Transfection with miR-181a-5p mimic promoted the proliferation of MTEC1 cells, but did not affect apoptosis. The effect was reversed when the expression of miR-181a-5p was suppressed in MTEC1 cells. Furthermore, the transforming growth factor beta receptor I (Tgfbr1) was confirmed as a direct target of miR-181a-5p by luciferase assay. Moreover, it was found that overexpression of miR-181a-5p down-regulated the phosphorylation of Smad3 and blocked the activation of the transforming growth factor beta signaling. Nevertheless, an inversely correlation was observed between the expression of Tgfbr1 and miR-181a-5p in TECs derived from mice of different age. Collectively, we provide evidence that miR-181a-5p may be an important endogenous regulator in the proliferation of TECs, and the expression levels of miR-181a-5p in TECs may be associated with the age-related thymus involution.

Integrated microRNA and mRNA sequencing analysis of age‐related changes to mouse thymic epithelial cells

“…miRNAs play key roles in the regulation of cellular processes like cell proliferation and ageing, and there is considerable evidence that they are crucial for thymic involution. For example, miR‐181a‐5p and miR‐195a‐5p in mouse TECs are involved in thymus ageing and involution via direct targeting of transforming growth factor β receptor 1 ( Tgfbr1 ) and Smad7 family member 7 ( Smad7 ), respectively . These data suggest that miRNAs are important regulators of thymic involution.…”

Age-related transcriptional modules and TF-miRNA-mRNA interactions in neonatal and infant human thymus

“…In addition, some of these abundantly expressed miRNAs were previously described as involved in relevant thymic functions. MiR-181a-5p expression is required for positive and negative thymocyte selection [50]; it was shown to regulate mTEC proliferation and age-related thymic involution in mice [51]. MiR-205-5p is highly expressed in mTECs and its expression changes correlate with thymic development and involution [52].…”

Minipuberty and Sexual Dimorphism in the Infant Human Thymus

“…MiR-150 controls the Notch pathway and influences T-cell development and physiology 17 . MiR-181 enhances cell proliferation in medullary thymic epithelial cells via regulating TGF-β signaling 18 and is involved in the positive and negative selection of T-cells 19 . MiR-342-3p is a well-known regulator of the NF-κB pathway 20 , whose activation was shown to be necessary for the thymic expression of Aire in mice 21,22 .…”