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Updated: Jun 5, 2026
In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
Published on: August 23, 2019
Mitogen-inducible gene-6 is a multifunctional adaptor protein with tumor suppressor-like activity in papillary
Chi-Iou Lin1, Jinyan Du, Wen T Shen
1Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Context:
Low tumoral expression of mitogen-inducible gene-6 (Mig-6) is associated with papillary thyroid cancer (PTC) recurrence after thyroidectomy.
Objective:
We hypothesize that Mig-6 behaves as a tumor suppressor in PTC.
Design:
Mig-6 expression and promoter methylation status were compared in 31 PTC specimens with matched normal thyroid tissue from the same patient. The impact of Mig-6 loss and gain of function on nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) activation, global tyrosine kinase phosphorylation, and cellular invasion was determined in vitro.
Results:
Mig-6 protein was abundant in all normal thyroid specimens, whereas 77% of PTC had low Mig-6 expression. Mig-6 promoter methylation was found in 79% of PTC with low Mig-6 expression. Low Mig-6 expression in PTC specimens was associated with low NF-κB activity but high levels of epidermal growth factor receptor (EGFR) and ERK phosphorylation. Mig-6 expression inversely correlated with PTC size but had no association with other clinicopathological variables including age, extrathyroidal extension, lymphovascular invasion, or histological subtype. Mig-6 knockdown in thyroid cancer cell lines resulted in EGFR phosphorylation and diminished NF-κB activity, whereas Mig-6 overexpression had the opposite effects. Mig-6 knockdown activated ErbB2, Met, and Src phosphorylation. Furthermore, Mig-6 regulated ERK phosphorylation independent from its effects on EGFR. Mig-6 knockdown promoted cellular proliferation, as determined by clonogenic survival. Lastly, Mig-6 knockdown increased matrix metalloproteinase-2 and -9 activities and increased cellular invasion.
Conclusions:
Mig-6 has tumor suppressor-like activity in PTC. In vivo studies are required to confirm that Mig-6 is a putative tumor suppressor in PTC, and future studies should investigate the utility of Mig-6 as a diagnostic marker.
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