title: HMGB1 induces the overexpression of miR-222 and miR-221 and increases             growth and motility in papillary thyroid cancer cells.
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.
authors.affiliation: Department of Experimental Medicine, Sapienza University of Rome, I-00161 Rome, Italy. stefania.mardente@uniroma1.it
authors.forename: Stefania
authors.initials: S
authors.lastname: Mardente
authors.forename: Emanuela
authors.initials: E
authors.lastname: Mari
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Consorti
authors.forename: Cira
authors.initials: C
authors.lastname: Di Gioia
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Negri
authors.forename: Marilena
authors.initials: M
authors.lastname: Etna
authors.forename: Alessandra
authors.initials: A
authors.lastname: Zicari
authors.forename: Alfredo
authors.initials: A
authors.lastname: Antonaci
mesh_terms: D000328:Adult; D000368:Aged; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism*; D002291:Carcinoma, Papillary; D002453:Cell Cycle; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D005260:Female; D024243:HMGB1 Protein / Q000378:metabolism*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D051059:PTEN Phosphohydrolase / Q000037:antagonists & inhibitors; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism; D015398:Signal Transduction; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000378:metabolism*
chemical_list: D024243:HMGB1 Protein; D035683:MicroRNAs; D051059:PTEN Phosphohydrolase; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; C525709:MIR221, human; C525710:MIR222, human; C494929:PTEN protein, human