Browse > Article
http://dx.doi.org/10.7314/APJCP.2015.16.17.7619

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)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.16, no.17, 2015 , pp. 7619-7625 More about this Journal
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;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Agrawal N, Frederick MJ, Pickering CR, et al (2011). Exome sequencing of head and neck squamous cell carcinoma reveals inactivating mutations in NOTCH1. Science, 333, 1154-7.   DOI
2 Aylon Y, Michael D, Shmueli A, et al (2006). A positive feedback loop between the p53 and Lats2 tumor suppressors prevents tetraploidization. Genes Dev, 20, 2687-700.   DOI
3 Bartel DP (2009). MicroRNAs: target recognition and regulatory functions. Cell, 136, 215-33.   DOI
4 Bommer GT, Gerin I, Feng Y, et al (2007). p53-mediated activation of miRNA34 candidate tumor-suppressor genes. Curr Biol, 17, 1298-307.   DOI
5 Bushati N, Cohen SM (2007). microRNA functions. Annu Rev Cell Dev Biol, 23, 175-205.   DOI
6 Cervigne NK, Reis PP, Machado J, et al (2009). Identification of a microRNA signature associated with progression of leukoplakia to oral carcinoma. Hum Mol Genet, 18, 4818-29.   DOI
7 Chang SS, Jiang WW, Smith I, et al (2008). MicroRNA alterations in head and neck squamous cell carcinoma. Int J Cancer, 123, 2791-7.   DOI
8 Chang TC, Wentzel EA, Kent OA, et al (2007). Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis. Mol Cell, 26, 745-52.   DOI
9 Chen D, Cabay RJ, Jin Y, et al (2013). MicroRNA Deregulations in Head and Neck Squamous Cell Carcinomas. J Oral Maxillofac Res, 4, e2.
10 Chen Z, Jin Y, Yu D, et al (2012). Down-regulation of the microRNA-99 family members in head and neck squamous cell carcinoma. Oral Oncol, 48, 686-91.   DOI
11 Childs G, Fazzari M, Kung G, et al (2009). Low-level expression of microRNAs let-7d and miR-205 are prognostic markers of head and neck squamous cell carcinoma. Am J Pathol, 174, 736-45.   DOI
12 Dikshit R, Gupta PC, Ramasundarahettige C, et al (2012). Cancer mortality in India: a nationally representative survey. Lancet, 379, 1807-16.   DOI
13 Doghman M, El Wakil A, Cardinaud B, et al (2010). Regulation of insulin-like growth factor-mammalian target of rapamycin signaling by microRNA in childhood adrenocortical tumors. Cancer Res, 70, 4666-75.   DOI
14 Feng Z, Zhang C, Wu R, et al (2011). Tumor suppressor p53 meets microRNAs. J Mol Cell Biol, 3, 44-50.   DOI
15 Feng Z, Zhang H, Levine AJ, et al (2005). The coordinate regulation of the p53 and mTOR pathways in cells. Proc Natl Acad Sci U S A, 102, 8204-9.   DOI
16 Ferlay J, Soerjomataram I, Dikshit R, et al (2015). Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer, 136, 359-86.   DOI
17 Friedman RC, Farh KK, Burge CB, et al (2009). Most mammalian mRNAs are conserved targets of microRNAs. Genome Res, 19, 92-105.
18 He L, He X, Lowe SW, et al (2007). microRNAs join the p53 network--another piece in the tumour-suppression puzzle. Nat Rev Cancer, 7, 819-22.   DOI
19 Hermeking H (2010). The miR-34 family in cancer and apoptosis. Cell Death Differ, 17, 193-9.   DOI
20 Hermeking H (2012). MicroRNAs in the p53 network: micromanagement of tumour suppression. Nat Rev Cancer, 12, 613-26.   DOI
21 Hu W, Chan CS, Wu R, et al (2010). Negative regulation of tumor suppressor p53 by microRNA miR-504. Mol Cell, 38, 689-99.   DOI
22 Hui AB, Lenarduzzi M, Krushel T, et al (2010). Comprehensive MicroRNA profiling for head and neck squamous cell carcinomas. Clin Cancer Res, 16, 1129-39.   DOI
23 India Project Team of the International Cancer Genome Consortium (2013). Mutational landscape of gingivo-buccal oral squamous cell carcinoma reveals new recurrentlymutated genes and molecular subgroups. Nat Commun, 4, 2873.   DOI
24 Kannan K, Munirajan AK, Krishnamurthy J, et al (1999). Low incidence of p53 mutations in betel quid and tobacco chewing-associated oral squamous carcinoma from India. Int J Oncol, 15, 1133-6.
25 Keklikoglou I, Koerner C, Schmidt C, et al (2012). MicroRNA-520/373 family functions as a tumor suppressor in estrogen receptor negative breast cancer by targeting NF-kappaB and TGF-beta signaling pathways. Oncogene, 31, 4150-63.   DOI
26 Kikkawa N, Kinoshita T, Nohata N, et al (2014). microRNA-504 inhibits cancer cell proliferation via targeting CDK6 in hypopharyngeal squamous cell carcinoma. Int J Oncol, 44, 2085-92.   DOI
27 Lajer CB, Nielsen FC, Friis-Hansen L, et al (2011). Different miRNA signatures of oral and pharyngeal squamous cell carcinomas: a prospective translational study. Br J Cancer, 104, 830-40.   DOI
28 Lane DP (1992). Cancer. p53, guardian of the genome. Nature, 358, 15-6.   DOI
29 Levine AJ, Feng Z, Mak TW, et al (2006). Coordination and communication between the p53 and IGF-1-AKT-TOR signal transduction pathways. Genes Dev, 20, 267-75.   DOI
30 Lee KH, Goan YG, Hsiao M, et al (2009). MicroRNA-373 (miR-373) post-transcriptionally regulates large tumor suppressor, homolog 2 (LATS2) and stimulates proliferation in human esophageal cancer. Exp Cell Res, 315, 2529-38.   DOI
31 Lewis BP, Burge CB, Bartel DP (2005). Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell, 120, 15-20.   DOI
32 Livak KJ, Schmittgen TD (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods, 25, 402-8.   DOI
33 Lui WO, Pourmand N, Patterson BK, et al (2007). Patterns of known and novel small RNAs in human cervical cancer. Cancer Res, 67, 6031-43.   DOI
34 Mandke P, Wyatt N, Fraser J, et al (2012). MicroRNA-34a modulates MDM4 expression via a target site in the open reading frame. PLoS One, 7, e42034.   DOI
35 Meng F, Glaser SS, Francis H, et al (2012). Epigenetic regulation of miR-34a expression in alcoholic liver injury. Am J Pathol, 181, 804-17.   DOI
36 Nelson KM, Weiss GJ (2008). MicroRNAs and cancer: past, present, and potential future. Mol Cancer Ther, 7, 3655-60.   DOI
37 Ng EK, Li R, Shin VY, et al (2014). MicroRNA-143 is downregulated in breast cancer and regulates DNA methyltransferases 3A in breast cancer cells. Tumour Biol, 35, 2591-8.   DOI
38 Parkin DM, Bray F, Ferlay J, et al (2005). Global cancer statistics, 2002. CA Cancer J Clin, 55, 74-108.   DOI
39 Noguchi S, Yasui Y, Iwasaki J, et al (2013). Replacement treatment with microRNA-143 and -145 induces synergistic inhibition of the growth of human bladder cancer cells by regulating PI3K/Akt and MAPK signaling pathways. Cancer Lett, 328, 353-61.   DOI
40 Nohata N, Hanazawa T, Kinoshita T, et al (2013). MicroRNAs function as tumor suppressors or oncogenes: aberrant expression of microRNAs in head and neck squamous cell carcinoma. Auris Nasus Larynx, 40, 143-9.   DOI
41 Pickering CR, Zhang J, Yoo SY, et al (2013). Integrative genomic characterization of oral squamous cell carcinoma identifies frequent somatic drivers. Cancer Discov, 3, 770-81.   DOI
42 Raver-Shapira N, Marciano E, Meiri E, et al (2007). Transcriptional activation of miR-34a contributes to p53-mediated apoptosis. Mol Cell, 26, 731-43.   DOI
43 Saranath D, Tandle AT, Teni TR, et al (1999). p53 inactivation in chewing tobacco-induced oral cancers and leukoplakias from India. Oral Oncol, 35, 242-50.   DOI
44 Scapoli L, Palmieri A, Lo Muzio L, et al (2010). MicroRNA expression profiling of oral carcinoma identifies new markers of tumor progression. Int J Immunopathol Pharmacol, 23, 1229-34.   DOI
45 Shiiba M, Uzawa K, Tanzawa H (2010). MicroRNAs in Head and Neck Squamous Cell Carcinoma (HNSCC) and Oral Squamous Cell Carcinoma (OSCC). Cancers (Basel), 2, 653-69.   DOI
46 Stransky N, Egloff AM, Tward AD, et al (2011). The mutational landscape of head and neck squamous cell carcinoma. Science, 333, 1157-60.   DOI
47 Volinia S, Galasso M, Costinean S, et al (2010). Reprogramming of miRNA networks in cancer and leukemia. Genome Res, 20, 589-99.   DOI
48 Swarbrick A, Woods SL, Shaw A, et al (2010). miR-380-5p represses p53 to control cellular survival and is associated with poor outcome in MYCN-amplified neuroblastoma. Nat Med, 16, 1134-40.   DOI
49 Tazawa H, Tsuchiya N, Izumiya M, et al (2007). Tumorsuppressive miR-34a induces senescence-like growth arrest through modulation of the E2F pathway in human colon cancer cells. Proc Natl Acad Sci U S A, 104, 15472-7.   DOI
50 Tran N, McLean T, Zhang X, et al (2007). MicroRNA expression profiles in head and neck cancer cell lines. Biochem Biophys Res Commun, 358, 12-7.   DOI
51 Voorhoeve PM, le Sage C, Schrier M, et al (2006). A genetic screen implicates miRNA-372 and miRNA-373 as oncogenes in testicular germ cell tumors. Cell, 124, 1169-81.   DOI
52 Wong TS, Liu XB, Wong BY, et al (2008). Mature miR-184 as Potential Oncogenic microRNA of Squamous Cell Carcinoma of Tongue. Clin Cancer Res, 14, 2588-92.   DOI
53 Yamakuchi M, Ferlito M, Lowenstein CJ (2008). miR-34a repression of SIRT1 regulates apoptosis. Proc Natl Acad Sci U S A, 105, 13421-6.   DOI
54 Yan B, Fu Q, Lai L, et al (2012). Downregulation of microRNA 99a in oral squamous cell carcinomas contributes to the growth and survival of oral cancer cells. Mol Med Rep, 6, 675-81.
55 Yang MH, Lin BR, Chang CH, et al (2012). Connective tissue growth factor modulates oral squamous cell carcinoma invasion by activating a miR-504/FOXP1 signalling. Oncogene, 31, 2401-11.   DOI
56 Zhang J, Sun Q, Zhang Z, et al (2013a). Loss of microRNA-143/145 disturbs cellular growth and apoptosis of human epithelial cancers by impairing the MDM2-p53 feedback loop. Oncogene, 32, 61-9.   DOI
57 Yen YC, Shiah SG, Chu HC, et al (2014). Reciprocal regulation of microRNA-99a and insulin-like growth factor I receptor signaling in oral squamous cell carcinoma cells. Mol Cancer, 13, 6.   DOI
58 Yu T, Wang XY, Gong RG, et al (2009). The expression profile of microRNAs in a model of 7,12-dimethyl-benz[a]anthranceinduced oral carcinogenesis in Syrian hamster. J Exp Clin Cancer Res, 28, 64.   DOI
59 Zanaruddin SN, Yee PS, Hor SY, et al (2013). Common oncogenic mutations are infrequent in oral squamous cell carcinoma of Asian origin. PLoS One, 8, e80229.   DOI
60 Zhang N, Su Y, Xu L (2013b). Targeting PKCepsilon by miR-143 regulates cell apoptosis in lung cancer. FEBS Lett, 587, 3661-7.   DOI