Genome Wide Expression Profiling of Cancer Cell Lines Cultured in Microgravity Reveals Significant Dysregulation of Cell Cycle and MicroRNA Gene Networks.
Prasanna Vidyasekar,Pavithra Shyamsunder,R. Arun,Rajalakshmi Santhakumar,Nand Kishore Kapadia,R. Ravi kumar,Rama Shanker Verma +6 more
TLDR
The genome wide expression profile 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.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.read more
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USP6 activation in nodular fasciitis by promoter-swapping gene fusions
Nimesh R. Patel,Nimesh R. Patel,John S.A. Chrisinger,Elizabeth G. Demicco,Stephen F. Sarabia,Jacquelyn Reuther,Erica Kumar,Andre M. Oliveira,Steven D. Billings,Judith V.M.G. Bovée,Angshumoy Roy,Alexander J. Lazar,Dolores Lopez-Terrada,Wei Lien Wang +13 more
TL;DR: The neoplastic nature of nodular fasciitis is confirmed, additional pathogenic fusion partners are defined, and a novel RT-PCR assay targets a single partner gene associated with fusions in bone and soft tissue tumors for agnostic detection of gene fusion partners.
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Modeling the Impact of Microgravity at the Cellular Level: Implications for Human Disease.
Peta Bradbury,Hanjie Wu,Jung Un Choi,Alan E. Rowan,Hongyu Zhang,Kate Poole,Jan Lauko,Joshua Chou +7 more
TL;DR: This review will examine recent insights into the impact of simulated microgravity on cell biology and how this technology may provide new insight into advancing the understanding of mechanically driven biology and disease.
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Influence of Microgravity on Apoptosis in Cells, Tissues, and Other Systems In Vivo and In Vitro.
Binod Prasad,Daniela Grimm,Sebastian M. Strauch,Gilmar Sidnei Erzinger,Thomas J. Corydon,Thomas J. Corydon,Michael Lebert,Nils E. Magnusson,Manfred Infanger,Peter Richter,Marcus Krüger +10 more
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Scaffold-free Tissue Formation Under Real and Simulated Microgravity Conditions.
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TL;DR: This MiniReview focuses on recent findings in the field of tissue engineering observed by exposing cells to real microgravity in space or to devices simulating to at least some extent microgravity conditions on Earth (ground-based facilities).
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PTEN/FOXO3/AKT pathway regulates cell death and mediates morphogenetic differentiation of Colorectal Cancer Cells under Simulated Microgravity
TL;DR: The regulation of cell function and viability under microgravity through PTEN/FOXO3/AKT pathway is highlighted to understand the three-dimensional (3D) biology of cancer in the aspect of stress response.
References
More filters
Journal ArticleDOI
Mechanisms of gene silencing by double-stranded RNA
Gunter Meister,Thomas Tuschl +1 more
TL;DR: A key step in known silencing pathways is the processing of dsRNAs into short RNA duplexes of characteristic size and structure, which guide RNA silencing by specific and distinct mechanisms.
Journal ArticleDOI
IL-6 and Stat3 Are Required for Survival of Intestinal Epithelial Cells and Development of Colitis-Associated Cancer
Sergei I. Grivennikov,Eliad Karin,Janoš Terzić,Janoš Terzić,Daniel Mucida,Guann-Yi Yu,Sivakumar Vallabhapurapu,Jürgen Scheller,Stefan Rose-John,Hilde Cheroutre,Lars Eckmann,Michael Karin +11 more
TL;DR: It is demonstrated that IL-6 is a critical tumor promoter during early CAC tumorigenesis and the NF-kappaB-IL-6-Stat3 cascade is an important regulator of the proliferation and survival of tumor-initiating IECs.
Journal ArticleDOI
MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer.
Irfan A. Asangani,Suhail Ahmed Kabeer Rasheed,D. A. Nikolova,Jörg H. Leupold,Nancy H. Colburn,Stefan Post,Heike Allgayer +6 more
TL;DR: This is the first study to show that Pdcd4 is negatively regulated by miR-21, and the first report to demonstrate that mi R-21 induces invasion/intravasation/metastasis.
PatentDOI
Smad proteins control drosha-mediated mirna maturation
TL;DR: In this paper, a CAGRN-motif that modifies expression of miRNAs that are regulated by the TGF-β/BMP signaling pathway was proposed.
Journal ArticleDOI
miRiad roles for the miR-17-92 cluster in development and disease
TL;DR: New work reveals essential functions for these miRNAs not only in tumor formation but also during normal development of the heart, lungs, and immune system.