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Down Regulation of miR-34a and miR-143 May Indirectly Inhibit p53 in Oral Squamous Cell Carcinoma: a Pilot Study

  • Manikandan, Mayakannan (Department of Genetics, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras) ;
  • Rao, Arunagiri Kuha Deva Magendhra (Department of Genetics, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras) ;
  • Arunkumar, Ganesan (Department of Genetics, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras) ;
  • Rajkumar, Kottayasamy Seenivasagam (Centre for Oncology, Government Royapettah Hospital & Kilpauk Medical College) ;
  • Rajaraman, Ramamurthy (Centre for Oncology, Government Royapettah Hospital & Kilpauk Medical College) ;
  • Munirajan, Arasambattu Kannan (Department of Genetics, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras)
  • Published : 2015.12.03

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. Materials and 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.

Keywords

MicroRNAs (miRNA);oral squamous cell carcinoma;head and neck cancer;tumor protein 53

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