title: Down Regulation of miR-34a and miR-143 May Indirectly Inhibit p53 in Oral Squamous Cell Carcinoma: a Pilot Study.
abstract: BACKGROUND
  Aberrant microRNA expression has been associated with the pathogenesis of a variety of human malignancies including oral squamous cell carcinoma (SCC). In this study, we examined primary oral SCCs for the expression of 6 candidate miRNAs, of which five (miR-34a, miR-143, miR-373, miR-380-5p, and miR- 504) regulate the tumor suppressor TP53 and one (miR-99a) is involved in AKT/mTOR signaling.
  
  
  METHODS
  Tumor tissues (punch biopsies) were collected from 52 oral cancer patients and as a control, 8 independent adjacent normal tissue samples were also obtained. After RNA isolation, we assessed the mature miRNA levels of the 6 selected candidates against RNU44 and RNU48 as endogenous controls, using specific TaqMan miRNA assays.
  
  
  RESULTS
  miR-34a, miR-99a, miR-143 and miR-380-5p were significantly down-regulated in tumors compared to controls. Moreover, high levels of miR-34a were associated with alcohol consumption while those of miR-99a and miR-143 were associated with advanced tumor size. No significant difference was observed in the levels of miR-504 between the tumors and controls whereas miR-373 was below the detection level in all but two tumor samples.
  
  
  CONCLUSIONS
  Low levels of miR-380-5p and miR-504 that directly target the 3'UTR of TP53 suggest that p53 may not be repressed by these two miRNAs in OSCC. On the other hand, low levels of miR-34a or miR-143 may relieve MDM4 and SIRT1 or MDM2 respectively, which will sequester p53 indicating an indirect mode of p53 suppression in oral tumors.
authors.affiliation: Department of Genetics, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras, Taramani Campus, India E-mail : akmunirajan@gmail.com, akmunirajan@unom.ac.in.
authors.forename: Mayakannan
authors.initials: M
authors.lastname: Manikandan
authors.forename: Arunagiri Kuha
authors.initials: AK
authors.lastname: Deva Magendhra Rao
authors.forename: Ganesan
authors.initials: G
authors.lastname: Arunkumar
authors.forename: Kottayasamy Seenivasagam
authors.initials: KS
authors.lastname: Rajkumar
authors.forename: Ramamurthy
authors.initials: R
authors.lastname: Rajaraman
authors.forename: Arasambattu Kannan
authors.initials: AK
authors.lastname: Munirajan
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D018797:Cell Cycle Proteins; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics; D010865:Pilot Projects; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics; D056564:Sirtuin 1 / Q000235:genetics; D000077195:Squamous Cell Carcinoma of Head and Neck; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors*
chemical_list: D020413:3' Untranslated Regions; D018797:Cell Cycle Proteins; C482775:MDM4 protein, human; C542359:MIRN143 microRNA, human; C522425:MIRN34 microRNA, human; D035683:MicroRNAs; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; C447939:SIRT1 protein, human; D056564:Sirtuin 1