A subset of microRNAs defining the side population of a human malignant mesothelioma cell line
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Myung-Chul Kim1,2, Na-Yon Kim1,2, Yu-Ri Seo1 and Yongbaek Kim1,3
1Laboratory of Clinical Pathology, College of Veterinary Medicine, Seoul National University, Gwanak-Gu, Seoul 151-742, The Republic of Korea
2BK21 PLUS Program for Creative Veterinary Science Research, College of Veterinary Medicine, Seoul National University, Gwanak-Gu, Seoul 151-742, The Republic of Korea
3Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Gwanak-Gu, Seoul 151-742, The Republic of Korea
Yongbaek Kim, email: [email protected]
Keywords: mesothelioma, side population, microRNA, intratumoral heterogeneity, microarray
Received: December 08, 2016 Accepted: March 22, 2017 Published: April 13, 2017
This study was performed to investigate the global expression profile of microRNAs in distinct subpopulations of a human malignant mesothelioma cell line. Total RNAs were isolated from the sorted side population and non-side population of MS1. The RNAs were subjected to analysis using Affymetrix GeneChip microRNA Arrays. After data extraction and normalization, a subset of microRNAs defining cell subpopulations was identified using bioinformatics softwares. Based on the criteria of 2-fold difference and the p-value of < 0.05, a total of 95 microRNAs were differentially expressed in the side population compared to the non-side population. Functional ontology revealed that target genes of the miRNAs were categorized into various gene ontology terms, such as stem cell maintenance, cell proliferation, programmed cell death, cell migration, and cellular response to stress. The Kyoto Encyclopedia of Genes and Genomes analysis showed that ErbB-2 receptor tyrosine kinases signaling pathway was the most represented. Integrated analysis of MiRTarBase and RNA-seq identified 12 target genes of microRNAs defining side population, including DDIT4 and ROCK2. The present study indicates that a distinct set of microRNAs may be critically involved in the generation and maintenance of heterogeneous subpopulations of cancer cells. They could be a plausible target for the eradication of more aggressive cancer cell subpopulations.
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