MicroRNA-125b Interacts with Foxp3 to Induce Autophagy in Thyroid Cancer

Mol Ther. 2018 Sep 5;26(9):2295-2303. doi: 10.1016/j.ymthe.2018.06.015. Epub 2018 Jun 21.

Abstract

Thyroid cancer is rapidly increasing in incidence worldwide. Although most thyroid cancer can be cured with surgery, radioactive iodine, and/or chemotherapy, thyroid cancers still recur and may become chemoresistant. Autophagy is a complex self-degradative process that plays a dual role in cancer development and progression. In this study, we found that miR-125b was downregulated in tissue samples of thyroid cancer as well as in thyroid cancer cell lines, and the expression of Foxp3 was upregulated. Further, we demonstrated that miR-125b could directly act on Foxp3 by binding to its 3' UTR and inhibit the expression of Foxp3. A negative relationship between miR-125b and Foxp3 was thus revealed. Overexpression of miR-125b markedly sensitized thyroid cancer cells to cisplatin treatment by inducing autophagy through an Atg7 pathway in vitro and in vivo. Taken together, our findings demonstrate a novel mechanism by which miR-125b has the potential to negatively regulate Foxp3 to promote autophagy and enhance the efficacy of cisplatin in thyroid cancer. miR-125 may be of therapeutic significance in thyroid cancer.

Keywords: Foxp3; autophagy; chemotherapy; miR-125b; thyroid cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / drug effects
  • 3' Untranslated Regions / genetics
  • Autophagy / drug effects*
  • Autophagy / genetics
  • Cell Line, Tumor
  • Cisplatin / pharmacology
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • In Vitro Techniques
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Thyroid Neoplasms / genetics
  • Thyroid Neoplasms / metabolism*

Substances

  • 3' Untranslated Regions
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • MIRN125 microRNA, human
  • MicroRNAs
  • Cisplatin