title: Expression level of miR-34a rather than P53 gene status correlates with mutability in related human lymphoblast cell lines.
abstract: The P53 gene is a tumor suppressor gene and can prevent mutation and tumor induction though apoptosis and DNA repair when it is activated by genotoxic stress. miR-34a expression is regulated by the P53 gene and might be required for cell response to DNA damage. TK6 cells are human lymphoblast cells with normal P53 function while WTK1 and NH32 cells derived from the same progenitor as TK6 cells are P53-deficient. Previous mutation research showed an unexpected result that NH32 cells were much less mutable than WTK1 cells, although the P53 gene in both the cell lines is not functional. To explore the possible mechanisms involved in the different mutability of the cell lines and relationship between P53 and miR-34a, we investigated the expression levels of miR-34a in the cells. The basal and X-ray-induced expression levels of miR-34a in TK6 and NH32 cells were much higher than those in WTK1 cells. The miR-34a was also able to be up-regulated to respond to X-ray exposure without a functional P53 gene in both of the NH32 and WTK1 cells. In addition, the expression levels of miR-34a in these three cell lines are inversely correlated well with their mutability: higher levels of miR-34a correspond with less mutable cells. These results suggest that alteration of miR-34a expression is at least partially independent of P53 regulation and its expression levels are closely related to cells' mutability regardless of P53 status.
authors.affiliation: Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, FDA, Jefferson, Arkansas, USA.
authors.forename: Xinrong
authors.initials: X
authors.lastname: Chen
authors.forename: Jian
authors.initials: J
authors.lastname: Yan
authors.forename: Tao
authors.initials: T
authors.lastname: Chen
mesh_terms: D002460:Cell Line; D004249:DNA Damage; D004307:Dose-Response Relationship, Radiation; D015870:Gene Expression; D006801:Humans; D008214:Lymphocytes / Q000166:cytology / Q000378:metabolism* / Q000528:radiation effects; D035683:MicroRNAs / Q000235:genetics*; D009154:Mutation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D014965:X-Rays
chemical_list: C522425:MIRN34 microRNA, human; D035683:MicroRNAs; D016159:Tumor Suppressor Protein p53