title: The effects of telomere shortening on cancer cells: a network model of proteomic and microRNA analysis.
abstract: Previously, we have shown that shortening of telomeres by telomerase inhibition sensitized cancer cells to cisplatinum, slowed their migration, increased DNA damage and impaired DNA repair. The mechanism behind these effects is not fully characterized. Its clarification could facilitate novel therapeutics development and may obviate the time consuming process of telomere shortening achieved by telomerase inhibition. Here we aimed to decipher the microRNA and proteomic profiling of cancer cells with shortened telomeres and identify the key mediators in telomere shortening-induced damage to those cells. Of 870 identified proteins, 98 were differentially expressed in shortened-telomere cells. 47 microRNAs were differentially expressed in these cells; some are implicated in growth arrest or act as oncogene repressors. The obtained data was used for a network construction, which provided us with nodal candidates that may mediate the shortened-telomere dependent features. These proteins' expression was experimentally validated, supporting their potential central role in this system.
authors.affiliation: FMRC, RMC, Sackler School of Medicine, Tel Aviv University, Israel. Electronic address: oritu@post.tau.ac.il.
authors.forename: O
authors.initials: O
authors.lastname: Uziel
authors.affiliation: School of Computer Science, Tel Aviv University, Israel.
authors.forename: N
authors.initials: N
authors.lastname: Yosef
authors.affiliation: School of Computer Science, Tel Aviv University, Israel.
authors.forename: R
authors.initials: R
authors.lastname: Sharan
authors.affiliation: School of Computer Science, Tel Aviv University, Israel.
authors.forename: E
authors.initials: E
authors.lastname: Ruppin
authors.affiliation: Department of Molecular Microbiology and Biotechnology, Tel Aviv University, Israel.
authors.forename: M
authors.initials: M
authors.lastname: Kupiec
authors.affiliation: Rosetta Genomics Ltd., Israel.
authors.forename: M
authors.initials: M
authors.lastname: Kushnir
authors.affiliation: FMRC, RMC, Sackler School of Medicine, Tel Aviv University, Israel.
authors.forename: E
authors.initials: E
authors.lastname: Beery
authors.affiliation: FMRC, RMC, Sackler School of Medicine, Tel Aviv University, Israel.
authors.forename: T
authors.initials: T
authors.lastname: Cohen-Diker
authors.affiliation: FMRC, RMC, Sackler School of Medicine, Tel Aviv University, Israel.
authors.forename: J
authors.initials: J
authors.lastname: Nordenberg
authors.affiliation: FMRC, RMC, Sackler School of Medicine, Tel Aviv University, Israel.
authors.forename: M
authors.initials: M
authors.lastname: Lahav
mesh_terms: D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D053263:Gene Regulatory Networks; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism*; D009841:Oligonucleotides / Q000494:pharmacology; D020543:Proteome / Q000032:analysis*; D040901:Proteomics; D059506:Telomere Shortening; D014407:Tumor Cells, Cultured
chemical_list: C479222:GRN163; D035683:MicroRNAs; D009841:Oligonucleotides; D020543:Proteome
keywords: Cancer cells; Functional networks; Proteomics; Telomeres