miR-574-3p inhibits proliferation and invasion in esophageal cancer by targeting FAM3C and MAPK1

Kaohsiung J Med Sci. 2020 May;36(5):318-327. doi: 10.1002/kjm2.12176. Epub 2019 Dec 27.

Abstract

Esophageal cancer is considered as one of the leading malignancies. MicroRNA-574-3p (miR-574-3p) was used as a postoperative prognostic indicator in patients with esophageal squamous cell carcinoma. However, the underlying mechanism miR-574-3p involvement in esophageal cancer remains unclear. In this study, the expression of miR-574-3p was reduced in esophageal cancer tissues and cells. In vitro, miR-574-3p mimics and inhibitor were transfected into esophageal cancer cells (TE-1 and TE-8 cells) to up- or downregulating of miR-574-3p. miR-574-3p inhibited proliferation, migration and invasion, and promoted apoptosis in esophageal cancer cells. In addition, miR-574-3p was confirmed to target family with sequence similarity 3 member C (FAM3C) and mitogen-activated protein kinase 1 (MAPK1). miR-574-3p suppressed phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) and rapidly accelerated fibrosarcoma (Raf)/mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling via regulating FAM3C and MAPK1. In vivo, overexpression of miR-574-3p suppressed tumor growth in mice. Our findings indicated that miR-574-3p repressed proliferation and invasion of esophageal cancer via regulation of FAM3C and MAPK1, which provides a new biomarker for esophageal cancer treatment.

Keywords: FAM3C; MAPK1 proliferation; esophageal cancer; invasion; miR-574-3p.

MeSH terms

  • Animals
  • Base Sequence
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Cytokines / genetics
  • Cytokines / metabolism*
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / pathology*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MAP Kinase Signaling System
  • Male
  • Mice, Inbred BALB C
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Mitogen-Activated Protein Kinase 1 / genetics
  • Mitogen-Activated Protein Kinase 1 / metabolism*
  • Mitogen-Activated Protein Kinase Kinases / metabolism
  • Neoplasm Invasiveness
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism

Substances

  • Cytokines
  • FAM3C protein, human
  • MIRN574 microRNA, human
  • MicroRNAs
  • Neoplasm Proteins
  • Proto-Oncogene Proteins c-akt
  • MAPK1 protein, human
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase Kinases