MicroRNA-663 suppresses cell invasion and migration by targeting transforming growth factor beta 1 in papillary thyroid carcinoma

Tumour Biol. 2016 Jun;37(6):7633-44. doi: 10.1007/s13277-015-4653-y. Epub 2015 Dec 19.

Abstract

MicroRNA-663 (miR-663) has been detected in a large variety of tumor types; however, it still holds both tumor suppressive and oncogenic roles in different tumor types. The miRNA-CHIP microarray assay revealed downregulation of miR-663 in papillary thyroid carcinoma (PTC); however, the effect of miR-663 on PTC cell invasion and migration remains unknown. Accordingly, this study aimed to investigate the potential involvement of miR-663 in PTC. In this study, miR-663 expression level was measured via quantitative real-time PCR in 91 pairs of human PTC and adjacent normal tissues and in two human PTC cell lines. The effect of miR-663 on PTC cell invasion and migration were studied by transwell and wound healing assays. In addition, the miR-663 target was searched and the underlying mechanism was clarified by reporter assay and rescue experiment. The current study confirmed that miR-663 expression was inhibited in PTC tissue samples and PTC cell lines. There were statistically significant differences in expression of miR-663 with regard to age and tumor size. Upregulation of miR-663 suppressed PTC cell invasion and migration. Further study showed that transforming growth factor beta 1 (TGFβ1) was the direct target of miR-663 and mediated the effect of miR-663 on PTC development. By targeting TGFβ1, miR-663 efficiently regulates the expression of epithelial-mesenchymal transition (EMT) markers and matrix metalloproteinases (MMPs). The data indicated that miR-663 may suppress tumor invasion and migration by targeting TGFβ1 and regulate EMT progress of PTC cells.

Keywords: Invasion; Migration; Papillary thyroid carcinoma; TGFβ1; miR-663.

MeSH terms

  • Adult
  • Carcinoma, Papillary / genetics*
  • Carcinoma, Papillary / pathology
  • Cell Line, Tumor
  • Cell Movement
  • Disease Progression
  • Down-Regulation
  • Epithelial-Mesenchymal Transition / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / physiology*
  • RNA Interference
  • RNA, Neoplasm / biosynthesis
  • RNA, Neoplasm / genetics*
  • RNA, Small Interfering / genetics
  • Thyroid Gland / metabolism
  • Thyroid Neoplasms / genetics*
  • Thyroid Neoplasms / pathology
  • Transforming Growth Factor beta1 / genetics
  • Transforming Growth Factor beta1 / physiology*

Substances

  • MIRN663 microRNA, human
  • MicroRNAs
  • Neoplasm Proteins
  • RNA, Neoplasm
  • RNA, Small Interfering
  • Transforming Growth Factor beta1