Association of miRNA-500 and AGE-RAGE axis in the development of thyroid cancer.

Worldwide, thyroid cancer is 7th most prevalent cancer, with projections indicating further increases by 2035. Few studies indicate role of micro RNA and RAGE receptor in cancer development. We hypothesize that micro RNA 500 may be associated with thyroid cancer development by effecting the AGE-RAGE axis. For the first time this study reported that miRNA-500 expression was higher in serum of subjects with papillary thyroid carcinoma (PTC) as compared to healthy controls. Similarly, higher levels of Advanced glycation end Products (AGEs) were seen and positively associated with mi-RNA500, in serum of PTC patients. While comparing the cancer and normal tissue of PTC patients we found enhanced expression of miRNA-500, RAGE receptor gene and protein in cancer tissue. RAGE ligands including HMGB-1 and S-100 were also found elevated in PTC cancer tissue as compared to normal tissue. In human thyroid cancer cells overexpressing miRNA-500 showed enhanced NFkB expression and oxidative stress however, this effect was diminished after blocking RAGE, linking miRNA-500 and RAGE together in development of thyroid cancer. Protein-protein interaction (PPI) pathway analysis further suggested that miR-500 target genes are embedded within a broader inflammatory signaling framework relevant to thyroid cancer biology. Our results demonstrate the association of miRNA-500 with RAGE axis along with preliminary evidence of pharmacological modulation, in thyroid cancer.