The number of red blood cells (RBCs) increases significantly in response to high-altitude hypoxic environments, and the RBC microRNA (miRNA) expression pattern is similar to that in whole blood. Studies have shown that miRNA in plasma can act as a circulating hypoxia-associated marker, but the effect of a high-altitude hypoxic environment on RBC-derived miRNAs has not yet been reported.

In a recent study, blood samples were collected from 20 Han Chinese individuals residing at 500 m (Sichuan Han), 10 migrant Han Chinese citizens residing at 3,658 m (Tibet Han) and 12 native Tibetans, and RBC indices measurements and miRNA sequencing analyses were performed for the three sample groups. The levels of some markedly altered miRNAs at high altitude were subsequently measured from 5 randomly selected samples of each group by real-time PCR. Bioinformatic analyses was performed to determine the potential target genes of selected hypoxia-associated miRNAs.

Marked changes of several RBC indices were observed among the Tibet Han population, the Tibetan population and the Sichuan Han population. A total of 516 miRNAs derived from RBCs were initially identified by miRNA sequencing in the three sample groups. Compared with the Sichuan Han population, 49 miRNAs were differentially expressed in the Tibet Han population (17 upregulated and 32 downregulated). 12 upregulated and 21 downregulated miRNAs were observed in the Tibetan population compared with the Sichuan Han population. A total of 40 RBC miRNAs were differentially expressed in the Tibetan population (15 upregulated and 25 downregulated) compared with the Tibet Han population. Two significantly altered miRNAs with the highest expression levels (miRNA-144-5p and miR-30b-5p) were selected for real-time PCR analysis, and the results were consistent with those of miRNA sequencing. Furthermore, bioinformatic analyses showed that some potential target genes of miR-144-5p and miR-30b-5p are involved in the erythroid- hypoxia-, and nitric oxide (NO)-related signaling pathways in response to hypoxia.

These findings provide clear evidence, for the first time, that a high-altitude hypoxic environment significantly affects human RBC miRNA profiles.

miRNA sequencing analysis of RBC miRNA profiles. miRNAs with more than 1 read in the sequencing data were considered expressed miRNAs. A Venn diagram (A) displays the overlapping miRNAs among the Sichuan Han group, Tibet Han group and Tibetan group. RBC miRNAs were compared between the Tibet Han group and the Sichuan Han group (B), between the Tibetan group and the Sichuan Han group (C), and between the Tibetan group and the Tibet Han group (D). The volcano plot displays the relationship between fold change and significance using a scatter plot view. The red dots in the plot represent significantly upregulated miRNAs, and the blue dots indicate significantly downregulated miRNAs.


L Sun, F Fan, R Li, B Niu, L Zhu, S Yu et al. (2018) Different Erythrocyte MicroRNA Profiles in Low-and High-Altitude Individuals Front Physiol doi: 10.3389/fphys.2018.01099 [article]

Microarray Profiling Identifies Novel Biomarkers and Therapeutic Targets for Gastric Cancer Metastasis FoxO6-Hippo Regulatory Pathway Controls Skull Growth and Face Morphology