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

Manikandan, Mayakannan; Rao, Arunagiri Kuha Deva Magendhra; Arunkumar, Ganesan; Rajkumar, Kottayasamy Seenivasagam; Rajaraman, Ramamurthy; Munirajan, Arasambattu Kannan

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저자정보: 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)

저널정보: 아시아태평양암예방학회 Asian Pacific journal of cancer prevention : APJCP Asian Pacific journal of cancer prevention : APJCP 제16권 제17호

발행연도: 2015.1

수록면: 7,619 - 7,625 (7page)

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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.

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

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Manikandan, Mayakannan

소속기관 Department of Genetics, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras