Red Blood Cells as Potential Repositories of MicroRNAs in the Circulatory System.

Liping Sun,Beifang Niu,Deqing Wang,Yang Yu

doi:10.3389/fgene.2020.00442

Abstract

The amount of erythrocyte-derived microRNAs (miRNAs) represents the majority of miRNAs expressed in whole blood. miR-451, miR-144, and miR-486, which are abundant in red blood cells (RBCs), are involved in the process of erythropoiesis and disease occurrence. Moreover, erythrocyte-derived miRNAs have been reported to be potential biomarkers of specific diseases. However, the function and underlying mechanisms of miRNAs derived from erythrocytes remain unclear. Based on a review of previously published literature, we discuss several possible pathways by which RBC miRNAs may function and propose that RBCs may serve as repositories of miRNAs in the circulatory system and participate in the regulation of gene expression mainly via the transfer of miRNAs from erythrocyte extracellular vesicles (EVs). In the whole blood, there are still other important cell types such as leukocytes and platelets harboring functional miRNAs, and hemolysis also exists, which limit the abundance of miRNAs as disease biomarkers, and thus, miRNA studies on RBCs may be impacted. In the future, the role of RBCs in the regulation of normal physiological functions of the body and the entire circulatory system under pathological states, if any, remains to be determined.

Highlights

Research studies conducted in the past decades have shown that that microRNAs play key roles in the process of erythropoiesis. Felli et al (2005) first separated CD34+ hematopoietic progenitor cells from umbilical cord blood and found that the expression levels of miR-221 and miR-222 sharply decreased with the differentiation of CD34+ hematopoietic progenitor cells
Recent research has shown that extracellular vesicles (EVs) released from red blood cells (RBCs) in large quantities during the blood phase of malarial infection are able to transfer human-derived Argonaute 2 (Ago2)– miRNAs complexes into the parasites within infected RBCs, which target the messenger RNAs (mRNAs) of a critical parasite antigen P. falciparum erythrocyte membrane protein-1 and downregulated its expression (Wang et al, 2017)
Recent studies have shown that bone marrow, lungs, liver, spleen, and kidneys may be potentially used as targets of RBC miRNAs based on the following evidence as follows: (1) RBCs contain several important miRNAs that are involved in erythropoiesis (Masaki et al, 2007; Fu et al, 2009; Randrianarison-Huetz et al, 2010; Xu et al, 2019); (2) lungs are the main oxygen exchange organs where a large amount of RBCs accumulate, and RBCs may be one of the cell types of which miRNAs are influenced in lung cancer (Leidinger et al, 2014); and (3) RBC-EVs are enriched in the liver, spleen, and kidney (Matsumoto et al, 2017), and RBC miRNAs are possibly involved in kidney-related diseases (Abraham et al, 2017; Fang et al, 2018)

Summary

Introduction

Research studies conducted in the past decades have shown that that microRNAs (miRNAs) play key roles in the process of erythropoiesis. Felli et al (2005) first separated CD34+ hematopoietic progenitor cells from umbilical cord blood and found that the expression levels of miR-221 and miR-222 sharply decreased with the differentiation of CD34+ hematopoietic progenitor cells.

Results

Conclusion