title: Tumor suppression by RNA from C/EBPβ 3'UTR through the inhibition of protein kinase Cε activity.
abstract: BACKGROUND
  Since the end of last century, RNAs from the 3'untranslated region (3'UTR) of several eukaryotic mRNAs have been found to exert tumor suppression activity when introduced into malignant cells independent of their whole mRNAs. In this study, we sought to determine the molecular mechanism of the tumor suppression activity of a short RNA from 3'UTR of C/EBPβ mRΝΑ (C/EBPβ 3'UTR RNA) in human hepatocarcinoma cells SMMC-7721.
  
  
  RESULTS
  By using Western blotting, immunocytochemistry, molecular beacon, confocal microscopy, protein kinase inhibitors and in vitro kinase assays, we found that, in the C/EBPβ 3'UTR-transfectant cells of SMMC-7721, the overexpressed C/EBPβ 3'UTR RNA induced reorganization of keratin 18 by binding to this keratin; that the C/EBPβ 3'UTR RNA also reduced phosphorylation and expression of keratin 18; and that the enzyme responsible for phosphorylating keratin 18 is protein kinase Cε. We then found that the C/EBPβ 3'UTR RNA directly inhibited the phosphorylating activity of protein kinase Cε; and that C/EBPβ 3'UTR RNA specifically bound with the protein kinase Cε-keratin 18 conjugate.
  
  
  CONCLUSIONS
  Together, these facts suggest that the tumor suppression in SMMC-7721 by C/EBPβ 3'UTR RNA is due to the inhibition of protein kinase Cε activity through direct physical interaction between C/EBPβ 3'UTR RNA and protein kinase Cε. These facts indicate that the 3'UTR of some eukaryotic mRNAs may function as regulators for genes other than their own.
authors.affiliation: State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Da-Quan
authors.initials: DQ
authors.lastname: Sun
authors.forename: Ding-Gan
authors.initials: DG
authors.lastname: Liu
mesh_terms: D020413:3' Untranslated Regions; D000970:Antineoplastic Agents / Q000494:pharmacology; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy; D045744:Cell Line, Tumor; D006801:Humans; D053538:Keratin-18 / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D051744:Protein Kinase C-epsilon / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012333:RNA, Messenger / Q000494:pharmacology*
chemical_list: D020413:3' Untranslated Regions; D000970:Antineoplastic Agents; D022782:CCAAT-Enhancer-Binding Protein-beta; C545012:CEBPB protein, human; C488421:KRT18 protein, human; D053538:Keratin-18; D012333:RNA, Messenger; D051744:Protein Kinase C-epsilon