Frequent Co-Expression of miRNA-5p and-3p Species and Cross-Targeting in Induced Pluripotent Stem Cells

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Title:	Frequent Co-Expression of miRNA-5p and-3p Species and Cross-Targeting in Induced Pluripotent Stem Cells
Authors:	Huang, Chiu-Jung Choo, Kong Bung Sugii, Shigeki Wee, Kenneth Cheong, Soon Keng Kamarul, Tunku
Contributors:	動物科學系
Keywords:	Induced pluripotent stem cells reprogramming miRNA-5p/3p species cell cycle control
Date:	2014
Issue Date:	2015-01-27 14:53:52 (UTC+8)
Abstract:	Background: A miRNA precursor generally gives rise to one major miRNA species derived from the 5' arm, and are called miRNA-5p. However, more recent studies have shown co-expression of miRNA-5p and -3p, albeit in different concentrations, in cancer cells targeting different sets of transcripts. Co-expression and regulation of the -5p and -3p miRNA species in stem cells, particularly in the reprogramming process, have not been studied. Methods: In this work, we investigated co-expression and regulation of miRNA-5p and -3p species in human induced pluripotent stem cells (iPSCs), mesenchymal stem cells (MSCs) and embryonic stem cells (ESC) using a nanoliter-scale real-time PCR microarray platform that included 1,036 miRNAs. Results: In comparing iPSC and ESC, only 32 miRNAs were found to be differentially expressed, in agreement of the ESC-like nature of iPSC. In the analysis of reprogramming process in iPSCs, 261 miRNAs were found to be differentially expressed compared with the parental MSC and pre-adipose tissue, indicating significant miRNA alternations in the reprogramming process. In iPSC reprogrammed from MSC, there were 88 miRNAs (33.7%), or 44 co-expressed 5p/3p pairs, clearly indicating frequent co-expression of both miRNA species on reprogramming. Of these, 40 pairs were either co-up-or co-downregulated indicating concerted 5p/3p regulation. The 5p/3p species of only 4 pairs were regulated in reverse directions. Furthermore, some 5p/3p species of the same miRNAs were found to target the same transcript and the same miRNA may cross-target different transcripts of proteins of the G1/S transition of the cell cycle; 5p/3p co-targeting was confirmed in stem-loop RT-PCR. Conclusion: The observed cross-and co-regulation by paired miRNA species suggests a fail-proof scheme of miRNA regulation in iPSC, which may be important to iPSC pluripotency.
Relation:	INTERNATIONAL JOURNAL OF MEDICAL SCIENCES 卷: 11 期: 8 頁碼: 824-833
Appears in Collections:	[Department of Animal Science] journal articles

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