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Int. J. Mol. Sci. 2018, 19(1), 87; doi:10.3390/ijms19010087

Integrated MicroRNA–mRNA Analysis Reveals miR-204 Inhibits Cell Proliferation in Gastric Cancer by Targeting CKS1B, CXCL1 and GPRC5A

1
Institute of Bioinformatics and Systems Biology, National Chiao Tung University, Hsinchu 300, Taiwan
2
Department of Biological Science and Technology, National Chiao Tung University, Hsinchu 300, Taiwan
3
Institute of Population Health Sciences, National Health Research Institutes, Miaoli 350, Taiwan
4
Institute of Molecular Medicine and Bioengineering, National Chiao Tung University, Hsinchu 300, Taiwan
5
Department of Medicine, Mackay Medical College, New Taipei City 252, Taiwan
6
Department of Obstetrics and Gynecology, Hsinchu Mackay Memorial Hospital, Hsinchu 300, Taiwan
7
Mackay Junior College of Medicine, Nursing and Management College, Taipei 112, Taiwan
8
Department of Medical Research, Hsinchu Mackay Memorial Hospital, Hsinchu 300, Taiwan
9
Division of Hepatology and Gastroenterology, Department of Internal Medicine, Hsinchu Mackay Memorial Hospital, Hsinchu 300, Taiwan
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 16 November 2017 / Revised: 23 December 2017 / Accepted: 25 December 2017 / Published: 28 December 2017
(This article belongs to the Collection Regulation by Non-Coding RNAs)
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Abstract

Gastric cancer (GC) is the second most frequent cause of cancer-related deaths worldwide. MicroRNAs are single-stranded RNA molecules of 21–23 nucleotides that regulate target gene expression through specific base-pairing interactions between miRNA and untranslated regions of targeted mRNAs. In this study, we generated a multistep approach for the integrated analysis of miRNA and mRNA expression. First, both miRNA and mRNA expression profiling datasets in gastric cancer from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) identified 79 and 1042 differentially expressed miRNAs and mRNAs, respectively, in gastric cancer. Second, inverse correlations between miRNA and mRNA expression levels identified 3206 miRNA–mRNA pairs combined with 79 dysregulated miRNAs and their 774 target mRNAs predicted by three prediction tools, miRanda, PITA, and RNAhybrid. Additionally, miR-204, which was found to be down-regulated in gastric cancer, was ectopically over-expressed in the AGS gastric cancer cell line and all down-regulated targets were identified by RNA sequencing (RNA-seq) analysis. Over-expression of miR-204 reduced the gastric cancer cell proliferation and suppressed the expression of three targets which were validated by qRT-PCR and luciferase assays. For the first time, we identified that CKS1B, CXCL1, and GPRC5A are putative targets of miR-204 and elucidated that miR-204 acted as potential tumor suppressor and, therefore, are useful as a promising therapeutic target for gastric cancer. View Full-Text
Keywords: microRNA (miRNA); integrated analysis; gastric cancer; expression profiling microRNA (miRNA); integrated analysis; gastric cancer; expression profiling
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MDPI and ACS Style

Shrestha, S.; Yang, C.-D.; Hong, H.-C.; Chou, C.-H.; Tai, C.-S.; Chiew, M.-Y.; Chen, W.-L.; Weng, S.-L.; Chen, C.-C.; Chang, Y.-A.; Lee, M.-L.; Huang, W.-Y.; Hsu, S.-D.; Chen, Y.-C.; Huang, H.-D. Integrated MicroRNA–mRNA Analysis Reveals miR-204 Inhibits Cell Proliferation in Gastric Cancer by Targeting CKS1B, CXCL1 and GPRC5A. Int. J. Mol. Sci. 2018, 19, 87.

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