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Evolution of the “autophagamiR”

MicroRNAs (miRs) are increasingly important diagnostic and prognostic markers in cancer but have not been defined in medullary thyroid carcinoma (MTC). MiR microarray profiling was performed on 19 primary MTC tumors, validated with qPCR in 45 cases and correlated with clinical outcomes. MiRs-183 and 375 were overexpressed and miR-9* underexpressed in sporadic vs. hereditary MTC (SMTC; HMTC). MiR-183 and 375 overexpression predicted lateral nodal metastases, residual disease, distant metastases and mortality. MiR-183 knockdown in an MTC cell line (TT cells) reduced cellular proliferation in association with elevated LC3B expression. This is suggestive of increased autophagic flux and potential cell death via autophagy induction. MiRs may subsequently be shown to serve as efficacious therapeutic strategies in MTC with a mechanism based upon autophagy.