A subset of microRNAs defining the side population of a human malignant mesothelioma cell line

Our plain-English summary of A subset of microRNAs defining the side population of a human malignant mesothelioma cell line, by M.C. Kim, N.Y. Kim, Y.R. Seo, et al (Oncotarget, 2017).

The study

• Authors: M.C. Kim, N.Y. Kim, Y.R. Seo, Y. Kim
• Journal: Oncotarget
• Published: 2017;8(26):42847-42856
• Cited by: 4 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

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.

In plain English

This was a laboratory study of one human malignant mesothelioma cell line, called MS1. It did not study patients or asbestos exposure. Using a dye test and cell sorting, the authors separated a small 'side population' of cells from the remaining 'non-side population' cells. They then measured microRNAs, small molecules that help control which genes are active, in both groups. They found 95 microRNAs that differed between the groups: 42 were higher and 53 were lower in the side population. A computer analysis of the genes these microRNAs are predicted to control pointed to processes such as cell growth, cell movement, cell death and responses to stress. The ErbB signaling pathway was among the most over-represented pathways. The authors combined these results with gene-activity data from the same sorted cells that they had published earlier, and identified 12 potential target genes. Lower miR-22 was paired with higher DDIT4, and higher miR-138 with lower ROCK2. The authors concluded that these changes may be associated with maintaining tumor heterogeneity. They noted that the study lacked validation experiments.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory (in vitro) study of a cell line: microRNA microarray comparison of sorted cell subpopulations, combined with computer target prediction and previously published RNA-seq data
• Who was studied: The human malignant mesothelioma cell line MS1, provided by Dr. Jablons (University of California San Francisco), sorted into side population (SP) and non-side population (NSP) cells. Three biological replicates of each were pooled.
• Exposure: No asbestos or other fiber exposure was studied. The comparison was between side population and non-side population cells of the same mesothelioma cell line.
• Main results:
  • 95 microRNAs differed (more than 2-fold, p less than 0.05) in side population cells compared with non-side population cells: 42 were up-regulated and 53 were down-regulated.
  • Gene Ontology analysis of 1,743 predicted target genes grouped them into processes including regulation of cell proliferation, gene expression, cell migration, cellular response to stress and the apoptotic process (programmed cell death).
  • KEGG pathway analysis found 37 signal transduction pathways significantly involved in side population cells compared with non-side population cells. The ErbB signaling pathway was one of the most over-represented.
  • Combining the microRNA results with RNA-seq data identified 12 potential target genes: 8 up-regulated mRNAs targeted by 3 down-regulated microRNAs, and 4 down-regulated mRNAs targeted by 3 up-regulated microRNAs.
  • Down-regulated miR-22 was paired with up-regulated DDIT4 (log2 fold change 2.296, p 0.047), and up-regulated miR-138 with down-regulated ROCK2 (log2 fold change -5.283, p 0.001), in side population cells. These were the two statistically significant inverse pairs.
• The authors' conclusion: The authors concluded that altered expression of miR-138 and miR-22 may be associated with maintaining tumor heterogeneity in human malignant mesothelioma by regulating their target genes, and that further functional validation is needed.
• Limitations the authors state:
  • The authors state that the study lacked a validation experiment.
  • The authors state that functional validation of the microRNA target genes is still needed.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Mesothelioma, P-Value, STEM.

Related studies

• Characterization of side population cells in human malignant mesothelioma cell lines — K. Kai, S. D'Costa, et al. (2010)
• An Integrated Analysis of the Genome-Wide Profiles of DNA Methylation and mRNA Expression Defining the Side Population of a Human Malignant Mesothelioma Cell Line — M.C. Kim, N.Y. Kim, et al. (2016)
• Inhibition of hedgehog signaling reduces the side population in human malignant mesothelioma cell lines — H.A. Kim, M.C. Kim, et al. (2015)
• Extensive temporal transcriptome and microRNA analyses identify molecular mechanisms underlying mitochondrial dysfunction induced by multi-walled carbon nanotubes in human lung cells — P. Nymark, P. Wijshoff, et al. (2015)
• Overexpression of microRNA‑486 affects the proliferation and chemosensitivity of mesothelioma cell lines by targeting PIM1 — S. Pinelli, R. Alinovi, et al. (2021)
• MicroRNAs dysregulation in human malignant pleural mesothelioma — V. Balatti, S. Maniero, et al. (2011)

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