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

Stephen Ohms, Jane E. Dahlstrom, Danny Rangasamy
2018 Gene Expression and Regulation in Mammalian Cells - Transcription Toward the Establishment of Novel Therapeutics  
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
more » ... rk 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.
doi:10.5772/intechopen.73266 fatcat:5p2tnqnngra4fcq6lyrycgsxce