miR-4443 targets TRIM14 to suppress metastasis and energy metabolism of papillary thyroid carcinoma (PTC) in vitro

Cell Biol Int. 2021 Sep;45(9):1917-1925. doi: 10.1002/cbin.11631. Epub 2021 Jul 12.

Abstract

Tripartite motif-containing protein 14 (TRIM14) is a tumor-promoter in papillary thyroid carcinoma (PTC). We found that miR-4443 expression was significantly downregulated in PTC tumor tissue, and was negatively associated with TRIM14. This study was designed to investigate the relationship between miR-4443 and TRIM14 on metastasis and energy metabolism in PTC and the underlying mechanisms. To this end, human PTC cells (SW1736 and MZ-CRC-1) were transfected with a miR-4443 mimic or miR-4443 inhibitor + siRNA-TRIM14, and then dual-luciferase assay, Transwell, Seahorse, and western blot analyses were performed to assess the function of miR-4443 and the underlying mechanism. We found that ectopic expression of miR-4443 inhibited PTC cell migration, invasion, ATP production, and aerobic glycolysis, while inhibition of miR-4443 had the opposite effect. miR-4443 directly targeted TRIM14 and reduced both TRIM14 mRNA and protein levels. Silencing TRIM14 significantly reversed miR-4443 inhibition-induced PTC cell migration, invasion, ATP production, aerobic glycolysis, and phosphorylation of the transcription factor STAT3. These findings suggest that miR-4443 is a tumor suppressor in PTC and inhibits metastasis and energy metabolism via the suppression of TRIM14 signaling.

Keywords: STAT3 signaling; glycolysis; microRNA; papillary thyroid carcinoma; tripartite motif-containing protein.

MeSH terms

  • Cell Line, Tumor
  • Cell Movement
  • Energy Metabolism
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • MicroRNAs / physiology*
  • Thyroid Cancer, Papillary / metabolism*
  • Thyroid Neoplasms / metabolism*
  • Tripartite Motif Proteins / metabolism*

Substances

  • Intracellular Signaling Peptides and Proteins
  • MIRN-4443 microRNA, human
  • MicroRNAs
  • TRIM14 protein, human
  • Tripartite Motif Proteins