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Genome wide expression profiling of cancer cell lines cultured in microgravity reveals significant dysregulation of cell cycle and MicroRNA gene networks
Prasanna Vidyasekar, Raj Pranap Arun, Rajalakshmi Santhakumar,
Published in Public Library of Science
2015
PMID: 26295583
Volume: 10
   
Issue: 8
Abstract

Zero gravity causes several changes in metabolic and functional aspects of the human body and experiments in space flight have demonstrated alterations in cancer growth and progression. This study reports the genome wide expression profiling of a colorectal cancer cell line-DLD-1, and a lymphoblast leukemic cell line-MOLT-4, under simulated microgravity in an effort to understand central processes and cellular functions that are dysregulated among both cell lines. Altered cell morphology, reduced cell viability and an aberrant cell cycle profile in comparison to their static controls were observed in both cell lines under microgravity. The process of cell cycle in DLD-1 cells was markedly affected with reduced viability, reduced colony forming ability, an apoptotic population and dysregulation of cell cycle genes, oncogenes, and cancer progression and prognostic markers. DNA microarray analysis revealed 1801 (upregulated) and 2542 (downregulated) genes (>2 fold) in DLD-1 cultures under microgravity while MOLT-4 cultures differentially expressed 349 (upregulated) and 444 (downregulated) genes (>2 fold) under microgravity. The loss in cell proliferative capacity was corroborated with the downregulation of the cell cycle process as demonstrated by functional clustering of DNA microarray data using gene ontology terms. The genome wide expression profile also showed significant dysregulation of post transcriptional gene silencing machinery and multiple microRNA host genes that are potential tumor suppressors and proto-oncogenes including MIR22HG, MIR17HG and MIR21HG. The MIR22HG, a tumor-suppressor gene was one of the highest upregulated genes in the microarray data showing a 4.4 log fold upregulation under microgravity. Real time PCR validated the dysregulation in the host gene by demonstrating a 4.18 log fold upregulation of the miR-22 microRNA. Microarray data also showed dysregulation of direct targets of miR-22, SP1, CDK6 and CCNA2. © 2015 Vidyasekar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

About the journal
JournalPLoS ONE
PublisherPublic Library of Science
ISSN19326203
Open AccessYes
Concepts (69)
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    CYCLIN A2
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    CYCLIN DEPENDENT KINASE 6
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    Microrna
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    MICRORNA 22
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    TRANSCRIPTION FACTOR SP1
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    Tumor marker
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    Cell cycle protein
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    ONCOPROTEIN
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    Apoptosis
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    Article
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    CANCER GROWTH
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    CANCER PROGNOSIS
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    CCNA2 GENE
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    CDK6 GENE
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    Cell activity
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    CELL CYCLE REGULATION
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    Cell population
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    Cell proliferation
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    Cell structure
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    CELL TRANSFORMATION
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    Cell viability
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    Colony formation
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    COLORECTAL CANCER CELL LINE
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    Controlled study
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    DLD 1 CELL LINE
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    Dna microarray
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    Down regulation
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    Gene control
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    Gene expression profiling
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    Gene ontology
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    Gene silencing
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    Gene targeting
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    Genome analysis
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    LEUKEMIA CELL LINE
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    Microgravity
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    MIR17HG GENE
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    MIR21HG GENE
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    MIR22HG GENE
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    MOLT 4 CELL LINE
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    ONCOGENE
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    Proto oncogene
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    Regulatory mechanism
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    Simulation
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    SP1 GENE
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    Transcription regulation
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    TUMOR SUPPRESSOR GENE
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    Upregulation
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    Cell cycle
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    Gene expression regulation
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    Gene regulatory network
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    Genetics
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    GENOME-WIDE ASSOCIATION STUDY
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    Human
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    HUMAN GENOME
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    Metabolism
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    Signal transduction
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    Tumor cell line
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    WEIGHTLESSNESS
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    Cell cycle proteins
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    Cell line, tumor
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    GENE EXPRESSION REGULATION, NEOPLASTIC
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    Gene regulatory networks
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    GENOME, HUMAN
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    GENOME-WIDE ASSOCIATION STUDY
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    Humans
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    Micrornas
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    Oligonucleotide array sequence analysis
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    PROTO-ONCOGENE PROTEINS
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    WEIGHTLESSNESS SIMULATION