Plant MIR167e-5p Inhibits Enterocyte Proliferation by Targeting β-Catenin.

Meng Li,Qing-Yan Jiang,Qian-Yun Xi,Jie Liu,Jia-Han Wu,Ting Chen,Jun-Yi Luo,Yong-Liang Zhang,Mei-Ying Xie,Bin Zeng,Jia-Jian He,Jia-Jie Sun,Hao-Jie Zhang,Rui-Song Ye

doi:10.3390/cells8111385

Abstract

MicroRNAs (miRNAs) are important negative regulators of genes involved in physiological and pathological processes in plants and animals. It is worth exploring whether plant miRNAs play a cross-kingdom regulatory role in animals. Herein, we found that plant MIR167e-5p regulates the proliferation of enterocytes in vitro. A porcine jejunum epithelial cell line (IPEC-J2) and a human colon carcinoma cell line (Caco-2) were treated with 0, 10, 20, and 40 pmol of synthetic 2′-O-methylated plant MIR167e-5p, followed by a treatment with 20 pmol of MIR167e-5p for 0, 24, 48, and 72 h. The cells were counted, and IPEC-J2 cell viability was determined by the MTT and EdU assays at different time points. The results showed that MIR167e-5p significantly inhibited the proliferation of enterocytes in a dose- and time-dependent manner. Bioinformatics prediction and a luciferase reporter assay indicated that MIR167e-5p targets β-catenin. In IPEC-J2 and Caco-2 cells, MIR167e-5p suppressed proliferation by downregulating β-catenin mRNA and protein levels. MIR167e-5p relieved this inhibition. Similar results were achieved for the β-catenin downstream target gene c-Myc and the proliferation-associated gene PCNA. This research demonstrates that plant MIR167e-5p can inhibit enterocyte proliferation by targeting the β-catenin pathway. More importantly, plant miRNAs may be a new class of bioactive molecules for epigenetic regulation in humans and animals.

Highlights

MicroRNAs are critical biological molecules and have attracted much attention for more than a decade
We found that plant MIR167e-5p could inhibit enterocyte proliferation and further identified β-catenin as a target of MIR167e-5p
Recent studies indicated that exosomes from plants can protect mice from colitis [12], and miRNAs can be packaged into Exosome-like nanoparticles (ELNs) to regulate the intestinal microbiota [13,15]

Summary

Introduction

MicroRNAs (miRNAs) are critical biological molecules and have attracted much attention for more than a decade. The functions of miRNA are well established in plants and animals. These single-stranded molecules impact on fundamental biological processes, including proliferation, differentiation, immune responses, and metabolism in different species. The recent detection of plant miRNAs in body fluids, including serum [1], urine [2], saliva [3], and milk [4], suggests that these endogenous circulating miRNAs may be broadly implicated in miRNA-mediated control of gene expression. Cells 2019, 8, 1385 have suggested that plant miRNAs might regulate gene expression in mammalian cells. Plant MIR2911 has been reported to target the PB2 and NS1 genes encoded by influenza A viruses (IAVs) H1N1, inhibiting H1N1 viral replication [6]. MIR159 is capable of inhibiting cancer proliferation by targeting T cell factor (TCF)

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Conclusion