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Genes 2017, 8(9), 213; doi:10.3390/genes8090213

5′-UTR and 3′-UTR Regulation of MICB Expression in Human Cancer Cells by Novel microRNAs

1
Biomedical Sciences Program, Graduates School of Khon Kaen University, Khon Kaen 40002, Thailand
2
Department of Clinical Immunology and Transfusion Sciences, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand
3
Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
4
The Centre for Research and Development of Medical Diagnostic Laboratories (CMDL), Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand
5
Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
*
Author to whom correspondence should be addressed.
Received: 14 July 2017 / Revised: 17 August 2017 / Accepted: 21 August 2017 / Published: 29 August 2017
(This article belongs to the Section Human Genomics and Genetic Diseases)
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Abstract

The treatment of cancer through the induction of natural killer group 2, member D (NKG2D) ligands is of interest, but understanding of mechanisms controlling expression of individual ligand is limited. The major histocompatibility complex (MHC) class I chain related protein B (MICB) is a member of NKG2D ligands. We aimed to investigate the role of 3′-untranslated (3′-UTR) and 5′-untranslated regions (5′-UTR) in post-transcriptional regulation of MICB. Nine novel microRNAs (miRNAs) predicted to interact with 3′-UTR and 5′-UTR using TargetScan, RNAhybrid and miBridge were identified. Their regulation of 3′-UTR, 5′-UTR and both 3′- and 5′-UTR sequences of MICB were indicated by the reduction of luciferase activities of luciferase reporter constructs. Mutations of miRNA binding sites at 3′- and 5′-UTRs resulted in increased luciferase activities confirming the regulation of nine candidate miRNAs. In addition, overexpression of candidate miRNAs also down-regulated the expression of reporter constructs. Consequently, the overexpression and inhibition of candidate miRNAs lead to the decreased and increased. MICB protein expressions on the cells tested, respectively. This study has identified a new role of miRNAs in regulation of MICB expression via both 3′-UTR and 5′-UTR sequences applicable for cancer immunotherapy. View Full-Text
Keywords: natural killer group 2, member D (NKG2D) ligands; natural killer group 2, member D (NKG2D); major histocompatibility complex (MHC) class I chain related protein B (MICB); microRNA; 5′-UTR regulation natural killer group 2, member D (NKG2D) ligands; natural killer group 2, member D (NKG2D); major histocompatibility complex (MHC) class I chain related protein B (MICB); microRNA; 5′-UTR regulation
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Wongfieng, W.; Jumnainsong, A.; Chamgramol, Y.; Sripa, B.; Leelayuwat, C. 5′-UTR and 3′-UTR Regulation of MICB Expression in Human Cancer Cells by Novel microRNAs. Genes 2017, 8, 213.

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