title: Development of cytotoxicity-sensitive human cells using overexpression of long non-coding RNAs.
abstract: Biosensors using live cells are analytical devices that have the advantage of being highly sensitive for their targets. Although attention has primarily focused on reporter gene assays using functional promoters, cell viability assays are still efficient. We focus on long non-coding RNAs (lncRNAs) that are involved in the molecular mechanisms associated with responses to cellular stresses as a new biological material. Here we have developed human live cells transfected with lncRNAs that can be used as an intelligent sensor of cytotoxicity for a broad range of environmental stresses. We identified three lncRNAs (GAS5, IDI2-AS1, and SNHG15) that responded to cycloheximide in HEK293 cells. Overexpression of these lncRNAs sensitized human cells to cell death in response to various stresses (cycloheximide, ultraviolet irradiation, mercury II chloride, or hydrogen peroxide). In particular, dual lncRNA (GAS5 plus IDI2-AS1, or GAS5 plus SNHG15) overexpression sensitized cells to cell death by more cellular stresses. We propose a method for highly sensitive biosensors using overexpression of lncRNAs that can potentially measure the cytotoxicity signals of various environmental stresses.
authors.affiliation: Research Institute for Environmental Management Technology, National Institute of Advanced Industrial Science and Technology (AIST), 16-1 Onogawa, Tsukuba, Ibaraki 305-8569, Japan. Electronic address: h.tani@aist.go.jp.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Tani
authors.affiliation: Research Institute for Environmental Management Technology, National Institute of Advanced Industrial Science and Technology (AIST), 16-1 Onogawa, Tsukuba, Ibaraki 305-8569, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Torimura
mesh_terms: D015374:Biosensing Techniques / Q000379:methods*; D016923:Cell Death / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002477:Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D003513:Cycloheximide / Q000633:toxicity; D003603:Cytotoxins / Q000633:toxicity*; D004249:DNA Damage / Q000528:radiation effects; D057809:HEK293 Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D017669:Mercury Compounds / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects; D062085:RNA, Long Noncoding / Q000235:genetics*; D013312:Stress, Physiological / Q000187:drug effects*; D014162:Transfection; D014466:Ultraviolet Rays
chemical_list: D003603:Cytotoxins; D017669:Mercury Compounds; D062085:RNA, Long Noncoding; D003513:Cycloheximide; D006861:Hydrogen Peroxide
keywords: Biosensor; Cellular stress; Cytotoxicity; Human cells; Non-coding RNA