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

Experimental and epidemiological studies have revealed that chronic inflammationcontributes to cancer progression and even predisposes to cellular transformation.Inflammatory infiltrates in papillary thyroid cancer include lymphocytes, macrophagesand cytokines. High-mobility group box 1 protein (HMGB1) is a late inflammatorycytokine that signals danger to the immune system through the receptor for advancedglycation end-products (RAGE) and Toll-like receptor. The activation of the abovereceptors results in the secretion of growth, chemotactic and angiogenic factorsthat contribute to chronic inflammation. In this study, we suggest that apartfrom the activation of signal transduction pathways by the activation of RAGE,the indirect inhibition of cell cycle regulators [such as phosphatase and tensinhomolog (PTEN)] may also cause an increase in cell growth and motility. MicroRNAs(miRNAs) have increasingly been implicated in regulating the malignant progressionof cancer. MiR-221 and miR-222 have been found to be deregulated in human papillarythyroid carcinomas. They are involved in cell proliferation through the inhibitionof 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 primarycultures of excised papillary lesions and in an established papillary cancer cellline (BC PAP). The overexpression of oncogenic miR-221 and miR-222 caused by HMGB1is associated with an increase in malignancy scores, namely cell growth and motility.