Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0135958
Title: Genome wide expression profiling of cancer cell lines cultured in microgravity reveals significant dysregulation of cell cycle and MicroRNA gene networks
Authors: Vidyasekar P.
Shyamsunder P. 
Arun R.
Santhakumar R.
Kapadia N.K.
Kumar R.
Verma R.S.
Keywords: cyclin A2
cyclin dependent kinase 6
microRNA
microRNA 22
transcription factor Sp1
tumor marker
cell cycle protein
oncoprotein
apoptosis
Article
cancer growth
cancer prognosis
CCNA2 gene
CDK6 gene
cell activity
cell cycle regulation
cell population
cell proliferation
cell structure
cell transformation
cell viability
colony formation
colorectal cancer cell line
controlled study
DLD 1 cell line
DNA microarray
down regulation
gene control
gene expression profiling
gene ontology
gene silencing
gene targeting
genome analysis
leukemia cell line
microgravity
MIR17HG gene
MIR21HG gene
MIR22HG gene
MOLT 4 cell line
oncogene
proto oncogene
regulatory mechanism
simulation
SP1 gene
transcription regulation
tumor suppressor gene
upregulation
cell cycle
gene expression profiling
gene expression regulation
gene regulatory network
genetics
genome-wide association study
human
human genome
metabolism
signal transduction
tumor cell line
weightlessness
Cell Cycle
Cell Cycle Proteins
Cell Line, Tumor
Cell Proliferation
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Gene Regulatory Networks
Genome, Human
Genome-Wide Association Study
Humans
MicroRNAs
Oligonucleotide Array Sequence Analysis
Proto-Oncogene Proteins
Signal Transduction
Weightlessness Simulation
Issue Date: 2015
Citation: Vidyasekar P., Shyamsunder P., Arun R., Santhakumar R., Kapadia N.K., Kumar R., Verma R.S. (2015). Genome wide expression profiling of cancer cell lines cultured in microgravity reveals significant dysregulation of cell cycle and MicroRNA gene networks. PLoS ONE 10 (8) : e0135958. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0135958
Rights: Attribution 4.0 International
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.
Source Title: PLoS ONE
URI: https://scholarbank.nus.edu.sg/handle/10635/161491
ISSN: 19326203
DOI: 10.1371/journal.pone.0135958
Rights: Attribution 4.0 International
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