title: mRNA export protein THOC5 as a tool for identification of target genes for cancer therapy.
abstract: Recent evidence indicates that mRNA export is selective, giving priority to a subset of mRNAs that control diverse biological processes including cell proliferation, differentiation, stress response, and cell survival as well as tumor development. The depletion of a member of the mRNA export complex, the THO complex, impairs the expression of only a subset of genes, but causes dramatic changes in phenotype, such as cell cycle inhibition, abnormal differentiation, and importantly apoptosis of stem cells and cancer cells but not normal epithelial cells, hepatocytes, or fibroblasts. Recent exosome sequence data revealed that over 100 driver gene mutations with a number of signaling pathways are involved in human cancer formation, indicating that multiple signaling pathways will need to be inhibited for cancer therapy. In this review we firstly describe a basic feature and function of the mRNA export complex, THO, secondly, the biological alteration upon depletion of a member of the THO complex in normal and cancer cells, and thirdly, identification of its target genes. Finally we describe our recent data on selection of targeting candidates from THOC5 dependent genes for application in cancer therapy.
authors.affiliation: Institut fuer Biochemie, OE4310, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, D-30623 Hannover, Germany.
authors.forename: Doan Duy Hai
authors.initials: DD
authors.lastname: Tran
authors.affiliation: Institut fuer Biochemie, OE4310, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, D-30623 Hannover, Germany.
authors.forename: Shashank
authors.initials: S
authors.lastname: Saran
authors.affiliation: Institut fuer Biochemie, OE4310, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, D-30623 Hannover, Germany.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Koch
authors.affiliation: Institut fuer Biochemie, OE4310, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, D-30623 Hannover, Germany. Electronic address: Tamura.Teruko@MH-Hannover.de.
authors.forename: Teruko
authors.initials: T
authors.lastname: Tamura
mesh_terms: D000818:Animals; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000628:therapy*; D009687:Nuclear Proteins / Q000502:physiology*; D034443:RNA Transport; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D009687:Nuclear Proteins; D012333:RNA, Messenger; C530378:THOC5 protein, human
keywords: Fine tuning genes; Target genes for cancer therapy; mRNA export complex