title: MicroRNA-383 regulates the apoptosis of tumor cells through targeting Gadd45g.
abstract: BACKGROUND
  MicroRNAs (miRNAs) are a class of small non-coding single-stranded RNA molecules that inhibit gene expression at post-transcriptional level. Gadd45g (growth arrest and DNA-damage-inducible 45 gamma) is a stress-response protein, which has been implicated in several biological processes, including DNA repair, the cell cycle and cell differentiation.
  
  
  RESULTS
  In this work, we found that miR-383 is a negative regulator of Gadd45g. Forced expression of miR-383 decreased the expression of Gadd45g through binding to the 3' untranslated region (3'-UTR), whereas inhibition of miR-383 increased Gadd45g expression. The presence of miR-383 increased the cellular sensitivity to DNA damage in breast cancer cells, which was rescued by ectopic expression of Gadd45g without the 3'-UTR. miR-383 also regulates the expression of Gadd45g in embryonic stem (ES) cells, but not their apoptosis under genotoxic stress. miR-383 was further showed to negatively regulate ES cell differentiation via targeting Gadd45g, which subsequently modulates the pluripotency-associated genes. Taken together, our study demonstrates that miR-383 is a negative regulator of Gadd45g in both tumor cells and ES cells, however, has distinct function in regulating cell apoptosis. miR-383 may be used as antineoplastic agents in cancer chemotherapy.
  
  
  CONCLUSIONS
  We demonstrate for the first time that miR-383 can specifically regulates the expression of Gadd45g by directly targeting to the 3-UTR region of Gadd45g mRNA, a regulatory process conserved in human tumor cells and mouse embryonic stem cells. These two compotents can be potentially used as antineoplastic agents in cancer chemotherapy.
authors.affiliation: Institute of Epigenetics and Cancer Research, Medical Science Building C-315, School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Transfusion Medicine, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai 200433, China.
authors.forename: Haihui
authors.initials: H
authors.lastname: Gu
authors.affiliation: Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Tongji University, 150 Jimo Road/1239 Siping Road, Shanghai 200120/200092, China.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Chang
authors.affiliation: Institute of Epigenetics and Cancer Research, Medical Science Building C-315, School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Junyu
authors.initials: J
authors.lastname: Wu
authors.affiliation: Institute of Epigenetics and Cancer Research, Medical Science Building C-315, School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Daliang
authors.initials: D
authors.lastname: Wang
authors.affiliation: Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Tongji University, 150 Jimo Road/1239 Siping Road, Shanghai 200120/200092, China.
authors.forename: Su
authors.initials: S
authors.lastname: Chen
authors.affiliation: Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Tongji University, 150 Jimo Road/1239 Siping Road, Shanghai 200120/200092, China.
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Transfusion Medicine, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai 200433, China.
authors.forename: Baohua
authors.initials: B
authors.lastname: Qian
mesh_terms: D020413:3' Untranslated Regions; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D002454:Cell Differentiation; D002945:Cisplatin / Q000494:pharmacology; D053595:Embryonic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D061986:MCF-7 Cells; D035683:MicroRNAs / Q000378:metabolism / Q000502:physiology*; D011485:Protein Binding; D014466:Ultraviolet Rays; D000097642:GADD45 Proteins
chemical_list: D020413:3' Untranslated Regions; D000970:Antineoplastic Agents; D002945:Cisplatin; D047908:Intracellular Signaling Peptides and Proteins; D035683:MicroRNAs; C485654:GADD45G protein, human; D000097642:GADD45 Proteins; C558685:MIRN383 microRNA, human