HMGB1 induces the overexpression of miR-222 and miR-221 and increases growth and motility in papillary thyroid cancer cells

Mardente,Stefania; Mari,Emanuela; Consorti,Fabrizio; Di Gioia,Cira; Negri,Rodolfo; Etna,Marilena; Zicari,Alessandra; Antonaci,Alfredo

doi:10.3892/or.2012.2058

HMGB1 induces the overexpression of miR-222 and miR-221 and increases growth and motility in papillary thyroid cancer cells

Authors:
- Stefania Mardente
- Emanuela Mari
- Fabrizio Consorti
- Cira Di Gioia
- Rodolfo Negri
- Marilena Etna
- Alessandra Zicari
- Alfredo Antonaci
View Affiliations

Affiliations: Department of Experimental Medicine, Sapienza University of Rome, I-00161 Rome, Italy, Department of Surgery ‘F. Durante’, Sapienza University of Rome, I-00161 Rome, Italy, Department of Radiology, Oncology and Pathology, Sapienza University of Rome, I-00161 Rome, Italy, Department of Biology and Biotechnology ‘Charles Darwin’, Sapienza University of Rome, I-00161 Rome, Italy
Published online on: September 26, 2012 https://doi.org/10.3892/or.2012.2058
Pages: 2285-2289

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Experimental and epidemiological studies have revealed that chronic inflammation contributes to cancer progression and even predisposes to cellular transformation. Inflammatory infiltrates in papillary thyroid cancer include lymphocytes, macrophages and cytokines. High-mobility group box 1 protein (HMGB1) is a late inflammatory cytokine that signals danger to the immune system through the receptor for advanced glycation end-products (RAGE) and Toll-like receptor. The activation of the above receptors results in the secretion of growth, chemotactic and angiogenic factors that contribute to chronic inflammation. In this study, we suggest that apart from the activation of signal transduction pathways by the activation of RAGE, the indirect inhibition of cell cycle regulators [such as phosphatase and tensin homolog (PTEN)] may also cause an increase in cell growth and motility. MicroRNAs (miRNAs) have increasingly been implicated in regulating the malignant progression of cancer. MiR-221 and miR-222 have been found to be deregulated in human papillary thyroid carcinomas. They are involved in cell proliferation through the inhibition of the cell cycle regulator, p27kip1, in human papillary carcinomas. In this study, we show that HMGB1 increases the expression of miR-221 and miR-222 in primary cultures of excised papillary lesions and in an established papillary cancer cell line (BC PAP). The overexpression of oncogenic miR-221 and miR-222 caused by HMGB1 is associated with an increase in malignancy scores, namely cell growth and motility.

View Figures

View References

1	Mardente S, Zicari A, Consorti F, Mari E, Di Vito M, Leopizzi M, Della Rocca C and Antonaci A: Cross-talk between NO and HMGB1 in limphocytic thyroiditis and papillary thyroid cancer. Oncol Rep. 24:1455–1461. 2010. View Article : Google Scholar : PubMed/NCBI
2	Pikarsky E, Porat RM, Stein I, Abramovitch R, Amit S, Kasem S, Gutkovich-Pyest E, Urieli-Shoval S, Galun E and Ben-Neriah Y: NF-κB funtions as a tumor promoter in inflammation-associated cancer. Nature. 431:261–266. 2004.
3	Mardente S, Lenti L, Lococo E, Consorti F, Della Rocca C, Romeo S, Misasi R and Antonaci A: Phenotypic and functional characterization of lymphocytes in autoimmune thyroiditis and in papillary carcinoma. Anticancer Res. 25:2483–2488. 2005.PubMed/NCBI
4	Van Beijnum JR, Buurman WA and Griffioen AW: Convergence and amplification of toll-like receptor (TLR) and receptor for advanced glycation end products (RAGE) signaling pathways via high mobility group B1 (HMGB1). Angiogenesis. 11:91–99. 2008.PubMed/NCBI
5	Galardi S, Mercatelli N, Farace MG and Ciafrè SA: NF-κB and c-Jun induce the expression of the oncogenic miR-221 and miR-222 in prostate carcinoma and glioblastoma cells. Nucleic Acids Res. 39:3892–3902. 2011.
6	Palumbo R, De Marchis F, Pusterla T, Conti A, Alessio M and Bianchi ME: Src family kinases are necessary for cell migration induced by extracelllular HMGB1. J Neurooncol. 86:617–623. 2009.PubMed/NCBI
7	Toure F, Zahm JM, Garnotel R, Lambert E, Bonnet N, Schmidt AM, Vitry F, Chanard J, Gillery P and Rieu P: Receptor for advanced glycation end-products (RAGE) modulates neutrophil adhesion and migration on glycoxidated extracellular matrix. Biochem J. 416:255–261. 2008. View Article : Google Scholar : PubMed/NCBI
8	Kim JY, Park HK, Yoon JS, Kim SJ, Kim ES, Ahn KS, Kim DS, Yoon SS, Kim BK and Lee YY: Advanced glycation end product (AGE)-induced proliferation of HEL cells via receptor for AGE-related signal pathways. Int J Oncol. 33:493–501. 2008.PubMed/NCBI
9	Maehama T and Dixon JE: PTEN: a tumour suppressor that functions asa phospholipid phosphatase. Trends Cell Biol. 9:125–128. 1999. View Article : Google Scholar : PubMed/NCBI
10	Si ML, Zhu S, Wu H, Wu F and Mo YY: miR-21-mediated tumor growth. Oncogene. 26:2799–2803. 2007. View Article : Google Scholar : PubMed/NCBI
11	Ma L, Teruya-Feldstein J and Weinberg RA: Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature. 449:682–688. 2007. View Article : Google Scholar : PubMed/NCBI
12	Bartel DP: MicroRNAs: target recognition and regulatory functions. Cell. 136:215–233. 2009. View Article : Google Scholar : PubMed/NCBI
13	He H, Jazdzewski K, Li W, Liyanarachchi S, Nagy R, Volinia S, Calin GA, Liu CG, Franssila K, Suster S, Kloos RT, Croce CM and de la Chapelle A: The role of microRNA genes in papillary thyroid carcinoma. Proc Natl Acad Sci USA. 102:1975–1980. 2005.
14	Visone R, Russo L, Pallante P, De Martino I, Ferraro A, Leone V, Borbone E, Petrocca F, Alder H, Croce CM and Fusco A: MicroRNAs (miR)-221 and miR-222, both overexpressed in human thyroid papillary carcinomas, regulate p27^Kip1 protein levels and cell cycle. Endocr Relat Cancer. 14:791–798. 2007. View Article : Google Scholar : PubMed/NCBI
15	Chun-Zhi Z, Lei H, An-Ling Z, Yan-Chao F, Xiao Y, Guang-Xiu W, Zhi-Fan J, Pei-Yu P, Qing-Yu Z and Chun-Sheng K: MicroRNA-221 and microRNA-222 regulate gastric carcinoma cell proliferation and radioresistance by targeting PTEN. BMC Cancer. 10:3672010. View Article : Google Scholar : PubMed/NCBI
16	Fabien N, Fusco A, Santoro M, Barbier Y, Dubois PM and Paulin C: Description of a human papillary thyroid carcinoma cell line. Morphologic study and expression of tumoral markers. Cancer. 15:2206–2212. 1994. View Article : Google Scholar
17	Hummel R, Hussey DJ and Haier J: MicroRNAs: predictors and modifiers of chemo- and radiotherapy in different tumour types. Eur J Cancer. 46:298–311. 2010. View Article : Google Scholar : PubMed/NCBI
18	Cully M, You H, Levine AJ and Mak TW: Beyond PTEN mutations: the PI3K pathway as an integrator of multiple inputs during tumorigenesis. Nat Rev Cancer. 6:184–192. 2006. View Article : Google Scholar : PubMed/NCBI
19	Li Q, Li M, Wang YL, Fauzee NJ, Yang Y, Pan J, Yang L and Lazar A: RNA interference of PARG could inhibit the metastatic potency of colon carcinoma cells via PI3-kinase/Akt pathway. Cell Physiol Biochem. 29:361–372. 2012. View Article : Google Scholar : PubMed/NCBI
20	Wong QW, Ching AK, Chan AW, Choy KW, To KF, Lai PB and Wong N: MiR-222 overexpression confers cell migratory advantages in hepatocellular carcinoma through enhancing AKT signaling. Clin Cancer Res. 16:867–875. 2010. View Article : Google Scholar : PubMed/NCBI
21	Kato M, Putta S, Wang M, Yuan H, Lanting L, Nair I, Gunn A, Nakagawa Y, Shimano H, Todorov I, Rossi JJ and Natarajan R: TGF-beta activates Akt kinase through a microRNA-dependent amplifying circuit targeting PTEN. Nat Cell Biol. 11:881–889. 2009. View Article : Google Scholar : PubMed/NCBI
22	Meng F, Henson R, Lang M, Wehbe H, Maheshwari S, Mendell JT, Jiang J, Schmittgen TD and Patel T: Involvement of human micro-RNA in growth and response to chemotherapy in human cholangiocarcinoma cell lines. Gastroenterology. 130:2113–2129. 2006. View Article : Google Scholar : PubMed/NCBI
23	Vincenti S, Brillante N, Lanza V, Bozzoni I, Presutti C, Chiani F, Etna MP and Negri R: HUVEC respond to radiation by inducing the expression of pro-angiogenic microRNAs. Radiat Res. 175:535–546. 2011. View Article : Google Scholar : PubMed/NCBI