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. 2019 Mar;33(3):e22825.
doi: 10.1002/jcla.22825. Epub 2018 Nov 28.

Altered expression of circular RNAs in human placental chorionic plate-derived mesenchymal stem cells pretreated with hypoxia

Affiliations

Altered expression of circular RNAs in human placental chorionic plate-derived mesenchymal stem cells pretreated with hypoxia

Xunsha Sun et al. J Clin Lab Anal. 2019 Mar.

Abstract

Background: Hypoxic preconditioning alters the biological properties of mesenchymal stem cells (MSCs). It is not known whether this process has an effect on circular RNAs (circRNAs) in MSCs.

Methods: Human placental chorionic plate-derived MSCs (hpcpMSCs) isolated from the same placentae were classed into two groups: hypoxic pretreated (hypoxia) group and normally cultured (normoxia) group. The comparative circRNA microarray analysis was used to determine circRNAs expression and verified by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) in the two groups.

Results: One hundred and two differentially expressed circRNAs in the hypoxia group were found compared to that in the normoxia group (fold change >1.5-fold and P < 0.05). The expression levels of circRNAs by qRT-PCR were consistent with those evaluated by microarray analysis. Gene ontology (GO) analysis showed that the putative function of their target genes for those differentially expressed circRNAs was primarily involved in cell development and its differentiation and regulation. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that transcriptional misregulation in cancer and mitogen-activated protein kinase (MAPK) signaling pathway were the most significant. MAPK signaling pathway was found to be the core regulatory pathway triggered by hypoxia.

Conclusions: The results indicate that the altered expression of specific circRNAs in MSCs is associated with hypoxic preconditioning. This finding provides further exploration of underlying mechanisms of the characteristic changes of MSCs with hypoxic preconditioning.

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Figures

Figure 1
Figure 1
CircRNAs expression profiles in hypoxia group and normoxia group. A, Scatter plots of circRNAs expression profiles in hypoxia group and normoxia group. The values on the X and Y axes in the scatter plot are the normalized signal values of the samples (log2 scaled). The green lines correspond to 1.5‐fold changes. B, Volcano plots of circRNAs expression profiles in hypoxia group and normoxia group. Red dots represent differentially expressed circRNAs (fold change >1.5‐fold and P < 0.05). C, Heat map of circRNAs differentially expressed between hypoxia group and normoxia group
Figure 2
Figure 2
qRT‐PCR validation of expression levels of circRNAs identified by microarray analysis. The error bar stands for standard deviations
Figure 3
Figure 3
Top 10 significant GO biological processes of the target genes of miRNAs interacted with differentially expressed circRNAs
Figure 4
Figure 4
Top 10 significant KEGG pathway of the target genes of miRNAs interacted with differentially expressed circRNAs
Figure 5
Figure 5
Pathway‐pathway interaction network. A higher number of edges for a pathway indicate a greater degree of interconnection and a more central role within the network

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