Iodine Promotes Tumorigenesis of Thyroid Cancer by Suppressing Mir-422a and Up-Regulating MAPK1

Abstract

Background/Aims: Iodine may trigger tumorigenesis and development of thyroid carcinoma, but the mechanisms involved remained elusive. MicroRNA (MiRNAs) are known to be involved in each stage of cancer development; however, the role of miRNAs in iodine-induced tumorigenesis of thyroid carcinoma remained unknown. In this study, we aimed at investigating miRNA related signaling pathway in thyroid cancer cells. Methods: Levels of miRNAs and mRNAs were determined using RT-qPCR and proteins were quantified by western blotting. Cell migration and proliferation were checked using Transwell assay and CCK8 assay respectively. Tumor xenografts in nude mice were established by subcutaneous injection of cancer cells. Results: Mitogen activated protein kinase 1 (MAPK1) was significantly up-regulated, while miR-422a was down-regulated in thyroid cancer cells cultured with high iodine; miR-422a directly bound to the 3’UTR of MAPK1 mRNA. Moreover, miR-422a negatively regulated MAPK1 expression, and down-regulated miR-422a promoted proliferation and migration of TPC-1 cells. In vivo studies also confirmed that iodine promoted tumor growth by suppressing miR-422a and up-regulating MAPK1. Conclusions: Our study illustrates a new pathway comprising iodine, miRNA and MAPK1, and defines a novel mechanism in thyroid cancer.