title: microRNA-143 protects cells from DNA damage-induced killing by downregulating FHIT expression.
abstract: MicroRNAs (miRNAs) are posttranscriptional modulators of gene expression and play an important role in many developmental processes. Recent studies suggest roles of miRNAs in carcinogenesis. Fragile histidine triad (FHIT) gene deletion, methylation, and reduced Fhit protein expression occur in about 70% of human epithelial tumors and are clearly associated with tumor progression. Although it has been previously reported that Fhit(-/-)cells exhibit more resistance to multi-DNA damage inducers, including ionizing radiation, it remains unclear how miRNAs targeting FHIT in DNA damage response play the role. This study reports that miR-143 directly targets FHIT and that overexpression of miR-143 results in significant G2-phase arrest and protects cells from DNA damage-induced killing. These results indicate an association of FHIT gene inactivation with increased survival after DNA damage and also provide useful information for miRNA-based drug development in two directions: protect cells from DNA damage-induced killing and sensitize cells to radiation therapy.
authors.affiliation: Department of Medical Molecular Biology, Beijing Institute of Biotechnology, China.
authors.forename: Yu-Xiang
authors.initials: YX
authors.lastname: Lin
authors.forename: Fang
authors.initials: F
authors.lastname: Yu
authors.forename: Ning
authors.initials: N
authors.lastname: Gao
authors.forename: Ji-Po
authors.initials: JP
authors.lastname: Sheng
authors.forename: Jun-Zhi
authors.initials: JZ
authors.lastname: Qiu
authors.forename: Bao-Cheng
authors.initials: BC
authors.lastname: Hu
mesh_terms: D020413:3' Untranslated Regions; D017766:Acid Anhydride Hydrolases / Q000235:genetics*; D045744:Cell Line, Tumor; D002470:Cell Survival; D004249:DNA Damage; D004260:DNA Repair; D016195:G2 Phase; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism* / Q000494:pharmacology; D009363:Neoplasm Proteins / Q000235:genetics*; D011995:Recombination, Genetic; D012878:Skin Neoplasms / Q000378:metabolism*; D014162:Transfection; D000099170:Bis(5'-adenosyl)triphosphatase
chemical_list: D020413:3' Untranslated Regions; D017766:Acid Anhydride Hydrolases; D035683:MicroRNAs; D009363:Neoplasm Proteins; D000099170:Bis(5'-adenosyl)triphosphatase; C542359:MIRN143 microRNA, human