Up-Regulation of miR-34a by Zinc Deficiency

Abstract

Mild-to-moderate zinc deficiency is common throughout the world. The biochemical changes associated with zinc deficiency have been extensively studied. However, the study of the regulation of microRNAs expression by zinc has just begun. MicroRNAs play a significant role in the regulation of gene function by binding to complementary regions of specific target mRNAs. MicroRNAs whose expression is altered in response to low zinc may play a role in adaptive responses to low zinc. Herein, the effect of low zinc intake on the expression of miR-34a in intestine, liver and thymus was analyzed in mice. In addition, the effect of low and excess zinc on the expression of miR-34a was analyzed in human hepatoma cells HepG2. Mice fed a low zinc diet exhibited low zinc content in tibia and increased expression of zinc transporter Slc39a4 in intestine. Moreover, the expression of miR-34a was increased in intestine and thymus of zinc deficient mice. The expression of miR-34a was also increased in HepG2 cells grown in low zinc medium. However, the expression of this microRNA was not affected by excess zinc. The up-regulation of miR-34a associated with zinc deficiency could be part of an adaptive response to cues generated in cells under low zinc conditions such as oxidative stress and inflammation.