Genome Wide Expression Profiling of Cancer Cell Lines Cultured in Microgravity Reveals Significant Dysregulation of Cell Cycle and MicroRNA Gene Networks.
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...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2015-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4546578?pdf=render |
| _version_ | 1818279938732589056 |
|---|---|
| author | Prasanna Vidyasekar Pavithra Shyamsunder Rajpranap Arun Rajalakshmi Santhakumar Nand Kishore Kapadia Ravi Kumar Rama Shanker Verma |
| author_facet | Prasanna Vidyasekar Pavithra Shyamsunder Rajpranap Arun Rajalakshmi Santhakumar Nand Kishore Kapadia Ravi Kumar Rama Shanker Verma |
| author_sort | Prasanna Vidyasekar |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T23:41:17Z |
| format | Article |
| id | doaj.art-316cac5b69544f3780d90dae34aa0883 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-12T23:41:17Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-316cac5b69544f3780d90dae34aa08832022-12-22T00:07:08ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01108e013595810.1371/journal.pone.0135958Genome Wide Expression Profiling of Cancer Cell Lines Cultured in Microgravity Reveals Significant Dysregulation of Cell Cycle and MicroRNA Gene Networks.Prasanna VidyasekarPavithra ShyamsunderRajpranap ArunRajalakshmi SanthakumarNand Kishore KapadiaRavi KumarRama Shanker VermaZero 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.http://europepmc.org/articles/PMC4546578?pdf=render |
| spellingShingle | Prasanna Vidyasekar Pavithra Shyamsunder Rajpranap Arun Rajalakshmi Santhakumar Nand Kishore Kapadia Ravi Kumar Rama Shanker Verma Genome Wide Expression Profiling of Cancer Cell Lines Cultured in Microgravity Reveals Significant Dysregulation of Cell Cycle and MicroRNA Gene Networks. PLoS ONE |
| title | Genome Wide Expression Profiling of Cancer Cell Lines Cultured in Microgravity Reveals Significant Dysregulation of Cell Cycle and MicroRNA Gene Networks. |
| title_full | Genome Wide Expression Profiling of Cancer Cell Lines Cultured in Microgravity Reveals Significant Dysregulation of Cell Cycle and MicroRNA Gene Networks. |
| title_fullStr | Genome Wide Expression Profiling of Cancer Cell Lines Cultured in Microgravity Reveals Significant Dysregulation of Cell Cycle and MicroRNA Gene Networks. |
| title_full_unstemmed | Genome Wide Expression Profiling of Cancer Cell Lines Cultured in Microgravity Reveals Significant Dysregulation of Cell Cycle and MicroRNA Gene Networks. |
| title_short | Genome Wide Expression Profiling of Cancer Cell Lines Cultured in Microgravity Reveals Significant Dysregulation of Cell Cycle and MicroRNA Gene Networks. |
| title_sort | genome wide expression profiling of cancer cell lines cultured in microgravity reveals significant dysregulation of cell cycle and microrna gene networks |
| url | http://europepmc.org/articles/PMC4546578?pdf=render |
| work_keys_str_mv | AT prasannavidyasekar genomewideexpressionprofilingofcancercelllinesculturedinmicrogravityrevealssignificantdysregulationofcellcycleandmicrornagenenetworks AT pavithrashyamsunder genomewideexpressionprofilingofcancercelllinesculturedinmicrogravityrevealssignificantdysregulationofcellcycleandmicrornagenenetworks AT rajpranaparun genomewideexpressionprofilingofcancercelllinesculturedinmicrogravityrevealssignificantdysregulationofcellcycleandmicrornagenenetworks AT rajalakshmisanthakumar genomewideexpressionprofilingofcancercelllinesculturedinmicrogravityrevealssignificantdysregulationofcellcycleandmicrornagenenetworks AT nandkishorekapadia genomewideexpressionprofilingofcancercelllinesculturedinmicrogravityrevealssignificantdysregulationofcellcycleandmicrornagenenetworks AT ravikumar genomewideexpressionprofilingofcancercelllinesculturedinmicrogravityrevealssignificantdysregulationofcellcycleandmicrornagenenetworks AT ramashankerverma genomewideexpressionprofilingofcancercelllinesculturedinmicrogravityrevealssignificantdysregulationofcellcycleandmicrornagenenetworks |