title: Tumor suppressor micro RNA miR-145 and onco micro RNAs miR-21 and miR-222 expressions are differentially modulated by hepatitis B virus X protein in malignant hepatocytes.
abstract: BACKGROUND
  Hepatitis B Virus (HBV) X protein (HBx) is known to be involved in the initiation and progression of hepatocellular carcinoma (HCC) through modulation of host gene response. Alterations in miRNA expressions are frequently noted in HCC. This study is aimed to examine the role of HBx protein in the modulation of oncogenic miRNA-21, miRNA-222 and tumor suppressor miRNA-145 in malignant hepatocytes.
  
  
  METHODS
  Expressions of miRNA-21, miRNA-222 and miRNA-145 were measured in HepG2 cells transfected with HBx-plasmid (genotype D) and with full length HBV genome (genotype D) and also in stably HBV producing HepG2.2.15 cells using real time PCR. Their target mRNAs and proteins - PTEN, p27 and MAP3K - were analyzed by real time PCR and western blot respectively. miRNA expressions were measured after HBx/D mRNA specific siRNA treatment. The expressions of these miRNAs were analyzed in liver cirrhosis and HCC patients also.
  
  
  RESULTS
  The study revealed a down-regulation of miRNA-21 and miRNA-222 expressions in HBx transfected HepG2 cells, pUC-HBV 1.3 plasmid transfected HepG2 cells as well as in HepG2.2.15 cells. Down regulation of miRNA-21 and miRNA-222 expression was observed in patient serum samples. Down regulation of miRNA-145 expression was observed in HepG2 cells transiently transfected with HBx and pUC-HBV1.3 plasmid as well as in patient samples but the expression of miRNA-145 was increased in HepG2.2.15 cells. Target mRNA and protein expressions were modulated in HepG2 cells and in HepG2.2.15 cell line consistent with the modulation of miRNA expressions.
  
  
  CONCLUSIONS
  Thus, HBx protein differentially modulated the expression of miRNAs. The study throws light into possible way by which HBx protein acts through microRNA and thereby regulates host functioning. It might suggest new therapeutic strategies against hepatic cancer.
authors.forename: Manikankana
authors.initials: M
authors.lastname: Bandopadhyay
authors.forename: Arup
authors.initials: A
authors.lastname: Banerjee
authors.forename: Neelakshi
authors.initials: N
authors.lastname: Sarkar
authors.forename: Rajesh
authors.initials: R
authors.lastname: Panigrahi
authors.forename: Sibnarayan
authors.initials: S
authors.lastname: Datta
authors.forename: Ananya
authors.initials: A
authors.lastname: Pal
authors.forename: Shivram Prasad
authors.initials: SP
authors.lastname: Singh
authors.forename: Avik
authors.initials: A
authors.lastname: Biswas
authors.forename: Shekhar
authors.initials: S
authors.lastname: Chakrabarti
authors.affiliation: ICMR Virus Unit, Kolkata, GB-4, 1st floor, ID & BG Hospital Campus, 57, Dr, S C Banerjee Road, Beliaghata, Kolkata West Bengal, 700010, India. runugc@gmail.com.
authors.forename: Runu
authors.initials: R
authors.lastname: Chakravarty
mesh_terms: D000328:Adult; D005260:Female; D056945:Hep G2 Cells; D006515:Hepatitis B virus / Q000502:physiology; D018197:Hepatoblastoma / Q000235:genetics / Q000821:virology*; D006801:Humans; D008103:Liver Cirrhosis / Q000235:genetics / Q000821:virology*; D008113:Liver Neoplasms / Q000235:genetics / Q000821:virology*; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism*; D054334:Viral Regulatory and Accessory Proteins
chemical_list: D035683:MicroRNAs; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C541010:MIRN145 microRNA, human; C524940:MIRN21 microRNA, human; C525710:MIR222, human; C057628:hepatitis B virus X protein