title: Dendrosomal curcumin increases expression of the long non-coding RNA gene MEG3 via up-regulation of epi-miRs in hepatocellular cancer.
abstract: BACKGROUND
  Hepatocellular carcinoma is the fifth most common cancer worldwide, with poor prognosis and resistance to chemotherapy. This gives novel cancer treatment methods an overwhelming significance. Epigenetic therapy of cancer is useful in reversing some of the cancer defects because of reversibility of the epigenetic alterations. Non-protein coding transcripts are the major part of our transcriptome. MEG3 is a tumor suppressor long non-coding RNA being expressed in many normal tissues. Methylation of MEG3 promoter region elicits the decrease in its expression in hepatocellular cancer cells. Bioactive nutrients including curcumin offer great potential in altering DNA methylation status which is catalyzed via DNMT1, DNMT3A and 3B.
  
  
  OBJECTIVE
  Herein, we aimed to study RNA-based epigenetic effects of dendrosomal curcumin (DNC) on hepatocellular cancer (HCC).
  
  
  METHODS
  To this end miRNA-dependent regulation of MEG3 expression under treatment with DNC was studied by evaluating the modulatory involvement of miR-29a for DNMT3A and 3B and miR-185 for DNMT1.
  
  
  METHODS
  We evaluated DNC entrance to HCC cells with the use of fluorescent characteristics of curcumin. Next we performed the MTT assay to evaluate DNC and dendrosome effects on HCC cell viability. The coding and non-coding genes expression analyses were done using quantitative-PCR.
  
  
  RESULTS
  In result we found that the DNC dependent overexpression of miR-29a and miR-185 (P < 0.01) can down-regulate the expression of DNMT1, 3A and 3B (P < 0.05) and subsequently overexpresses MEG3 (P < 0.05).
  
  
  CONCLUSIONS
  DNC potentially can induce DNA hypomethylation and reexpression of silenced tumor suppressor genes in HCC. These data suggest that DNC could be an effective choice for epigenetic therapy of HCC.
authors: Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.
authors: Mina
authors: M
authors: Zamani
authors: Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran. Electronic address: sadeghma@modares.ac.ir.
authors: Majid
authors: M
authors: Sadeghizadeh
authors: Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.
authors: Mehrdad
authors: M
authors: Behmanesh
authors: Department of Resin and Additives, Institute for Color Science and Technology, Tehran, Iran.
authors: Farhood
authors: F
authors: Najafi
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000473:pathology; D045744:Cell Line, Tumor / Q000187:drug effects; D003474:Curcumin / Q000737:chemistry*; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D000090205:DNA Methyltransferase 3A; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells / Q000187:drug effects; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D000097584:DNA Methyltransferase 3B
chemical_list: D003474:Curcumin; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; D035683:MicroRNAs; D062085:RNA, Long Noncoding; D000097584:DNA Methyltransferase 3B; C000717967:DNMT3A protein, human; C498907:MEG3 non-coding RNA, human; C532045:MIRN29a microRNA, human; C000619380:DNMT1 protein, human
keywords: DNA methylation; Dendrosomal curcumin; Epigenetic therapy; Hepatocellular cancer; Long non-coding RNA; miRNA