Passenger or Driver: Can Gene Expression Profiling Tell Us Anything about LINE-1 in Cancer?

LINE-1 retrotransposons are expressed in epithelial cancers but not normal adult tissues. Previously, we demonstrated repression of cell proliferation, migration, and invasion genes in L1-reverse transcriptase-inhibited T47D cells, while genes involved in cell projection, formation of vacuolar membr...

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Main Authors: Ohms, Stephen (Author), Dahlstrom, Jane E. (Author), Rangasamy, Danny (Author)
Format: Ebooks
Published: IntechOpen, 2018-02-28.
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042 |a dc 
100 1 0 |a Ohms, Stephen  |e author 
700 1 0 |a Dahlstrom, Jane E.  |e author 
700 1 0 |a Rangasamy, Danny  |e author 
245 0 0 |a Passenger or Driver: Can Gene Expression Profiling Tell Us Anything about LINE-1 in Cancer? 
260 |b IntechOpen,   |c 2018-02-28. 
500 |a https://mts.intechopen.com/articles/show/title/passenger-or-driver-can-gene-expression-profiling-tell-us-anything-about-line-1-in-cancer- 
520 |a LINE-1 retrotransposons are expressed in epithelial cancers but not normal adult tissues. Previously, we demonstrated repression of cell proliferation, migration, and invasion genes in L1-reverse transcriptase-inhibited T47D cells, while genes involved in cell projection, formation of vacuolar membranes, and intercellular junctions were upregulated. Extending this, we examined microarray data from L1-silenced and Efavirenz-treated T47D cells by Weighted Gene Correlation Network Analysis and literature mining. Hub genes in the most significant module comparing L1-silenced and untreated controls included HSP90AB2p, DDX39A, PANK2, MT1M, and LIMK2. HSP90AB2p is related to HSP90, a master regulator of cancer, cancer evolvability and chemo-resistance. DDX39A is a known cancer driver gene while PANK2 and MT1M affect multiple pathways. LIMK2 and SYBL1 impact actin cytoskeletal dynamics and the cofilin pathway, cancer cell motility, and the epithelial-to-mesenchymal transition. Also affected were signal transduction, HIF1 pathways, iron/redox metabolism, stress granules and cancer stem cell-related metabolic reprogramming and the eIF4F translation initiation complex. Hub genes in other modules, including BTRC, MDM2, and FBXW7, stabilize oncoproteins like MYC, p53, and NOTCH1 or reflect CXCL12-CXCR4 signalling. Our findings support mounting evidence that L1 activity is a cause, rather than a consequence of oncogenesis, with L1 affecting the formation of cancer stem cells. 
540 |a https://creativecommons.org/licenses/by/3.0/ 
546 |a en 
690 |a Gene Expression and Regulation in Mammalian Cells - Transcription Toward the Establishment of Novel Therapeutics 
655 7 |a Chapter, Part Of Book  |2 local 
786 0 |n https://www.intechopen.com/books/7204 
787 0 |n ISBN:978-953-51-3867-9 
856 \ \ |u https://mts.intechopen.com/articles/show/title/passenger-or-driver-can-gene-expression-profiling-tell-us-anything-about-line-1-in-cancer-  |z Get Online