miR-454-3p promotes proliferation and induces apoptosis in human cervical cancer cells by targeting TRIM3

Biochem Biophys Res Commun. 2019 Aug 27;516(3):872-879. doi: 10.1016/j.bbrc.2019.06.126. Epub 2019 Jun 30.

Abstract

Abnormally expressed microRNAs have been demonstrated related to the development and progression of cervical cancer. However, the molecular mechanisms remain largely unkown. Here, we aimed to demonstrate the exact role of miR-454-3p in cervical cancer. Depletion of miR-454-3p in cervical cancer cells resulted in inhibition of cell growth and promotion of cell apoptosis. Bioinformatics analysis predicted that tripartite motif-containing 3 (TRIM3), a tumor suppressor gene in cervical cancer, is a promising target of miR-454-3p. Dual-luciferase reporter gene assay revealed that miR-454-3p directly target TIRM3 by binding to the 3'UTR of TIRM3. In cervical cancer cells (C-33A and SiHa) with endogenous low TRIM3 expression, decreased expression of miR-454-3p significantly elevated TRIM3 expression. In the cervical cancer cell (HeLa) with endogenous high TRIM3 expression, increased expression of miR-454-3p obviously inhibited TRIM3 expression and then manipulating cell growth and apoptosis, down-regulating the expression of P53 and cleaved caspase-3 via P38 MAPK signaling. Taken together, these findings demonstrated miR-454-3p as a cancer promoter by targeting TRIM3 in human cervical cancer.

Keywords: Cervical cancer; Hsa-miR-454-3p; TRIM3; Tumor promoter.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antagomirs / genetics
  • Antagomirs / metabolism
  • Apoptosis / genetics*
  • Base Sequence
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Cell Line, Tumor
  • Cell Proliferation
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Genes, Reporter
  • HeLa Cells
  • Humans
  • Imidazoles / pharmacology
  • Luciferases / genetics
  • Luciferases / metabolism
  • MicroRNAs / agonists
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Oligoribonucleotides / genetics
  • Oligoribonucleotides / metabolism
  • Pyridines / pharmacology
  • Signal Transduction
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • p38 Mitogen-Activated Protein Kinases / genetics*
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Antagomirs
  • Carrier Proteins
  • Imidazoles
  • MIRN454 microRNA, human
  • MicroRNAs
  • Oligoribonucleotides
  • Pyridines
  • TRIM3 protein, human
  • Luciferases
  • p38 Mitogen-Activated Protein Kinases
  • CASP3 protein, human
  • Caspase 3
  • SB 203580