MicroRNA-142-3P suppresses the progression of papillary thyroid carcinoma by targeting FN1 and inactivating FAK/ERK/PI3K signaling

Cell Signal. 2023 Sep:109:110792. doi: 10.1016/j.cellsig.2023.110792. Epub 2023 Jul 3.

Abstract

Objectives: miR-142-3P is a tumor suppressor in various malignant cancers. However, the function of miR-142-3P in papillary thyroid carcinoma (PTC) remains to be elucidated. The aim of this study was to explore the function and mechanism of miR-142-3P in PTC.

Methods: Real Time Quantitative PCR (RT-qPCR) was used to assess the expression of miR-142-3P and Fibronectin 1 (FN1) in PTC. The correlation between FN1 and miR-142-3P expression was analyzed by Spearman's correlation analysis. Cell Counting Kit 8 (CCK8), 5-ethynyl-2'-deoxyuridine (EDU) assay, cell migration and invasion assay and wound healing measures evaluated the effect of miR-142-3P and FN1 on cell proliferation, migration and invasion. Dural Luciferase reported gene assay evaluated the interaction between miR-142-3P and 3' untranslated region (UTR) of FN1. The Epithelial-Mesenchymal-Transition (EMT) and apoptosis related marker genes were measured using western blot analysis (WB).

Results: miR-142-3P was significantly decreased in both PTC specimens and relevant cell lines. Functionally, miR-142-3P inhibited cell proliferation, migration, invasion and EMT, and induced the cell apoptosis in PTC. In addition, miR-142-3P bound directly with 3' UTR of FN1 and negatively regulated the expression of FN1 in PTC. FN1 expression is elevated in PTC, and its aberrant high correlated with declines in recurrence-free survival (RFS). Moreover, FN1 promoted cell proliferation, migration, invasion and EMT, induced cell apoptosis in PTC cells. Depletion of FN1 rescues the effect of miR-142-3P inhibitor on cell proliferation, invasion, apoptosis and EMT via inactivating Focal Adhesion Kinase (FAK)/Extracellular Signal-Regulated Kinase (ERK) / Phosphoinostide 3-kinase (P13K) signaling.

Conclusion: miR-142-3P suppressed cell proliferation, migration, invasion and EMT through modulating FN1/FAK/ERK/PI3K signaling in PTC, suggesting it as a potential therapeutic target for PTC.

Keywords: FAK signaling; FN1; Invasion; Thyroid cancer; miR-142–3P.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Fibronectins / metabolism
  • Focal Adhesion Protein-Tyrosine Kinases / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs* / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Thyroid Cancer, Papillary / genetics
  • Thyroid Cancer, Papillary / metabolism
  • Thyroid Neoplasms* / pathology

Substances

  • MicroRNAs
  • Phosphatidylinositol 3-Kinases
  • Fibronectins
  • Focal Adhesion Protein-Tyrosine Kinases
  • MIRN142 microRNA, human