Integrated microRNA–mRNA analysis reveals miR-204 inhibits cell proliferation in gastric cancer by targeting CKS1B, CXCL1 and GPRC5A

Sirjana Shrestha, Chi Dung Yang, Hsiao Chin Hong, Chih Hung Chou, Chun San Tai, Men Yee Chiew, Wen-Liang Chen, Shun Long Weng, Chung Chu Chen, Yi An Chang, Meng Lin Lee, Wei Yun Huang, Sheng Da Hsu, Yi Chang Chen, Hsien Da Huang*

*Corresponding author for this work

Research output: Contribution to journalArticle

19 Scopus citations

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.

Original languageEnglish
Article number87
JournalInternational journal of molecular sciences
Volume19
Issue number1
DOIs
StatePublished - 1 Jan 2018

Keywords

  • Expression profiling
  • Gastric cancer
  • Integrated analysis
  • MicroRNA (miRNA)

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    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. (2018). Integrated microRNA–mRNA analysis reveals miR-204 inhibits cell proliferation in gastric cancer by targeting CKS1B, CXCL1 and GPRC5A. International journal of molecular sciences, 19(1), [87]. https://doi.org/10.3390/ijms19010087