MiR-29a inhibits invasion and metastasis of cervical cancer via modulating methylation of tumor suppressor SOCS1

Future Oncol. 2019 May;15(15):1729-1744. doi: 10.2217/fon-2018-0497. Epub 2019 Apr 30.

Abstract

Aims: To investigate roles of miR-29a-DNMT1-SOCS1 axis in cervical cancer invasion and migration. Materials & methods: The methylation level of SOCS1 was determined by methylation specific PCR. The cell apoptosis, proliferation, migration and invasion were examined by Annexin-V/PI staining, MTT and colony formation assays, plus scratch and transwell assays respectively. The expressions of epithelial-mesenchymal transition and NF-κB related proteins were determined by western blotting. Results: MiR-29a was downregulated, accompanied with DNMT1 upregulation and SOCS1 downregulation in cervical cancer tissues. MiR-29a suppressed DNMT1, inhibited SOCS1 promoter methylation and upregulated its expression. Moreover, miR-29a promoted cell apoptosis, suppressed proliferation, inhibited migration and invasion via inactivation of NF-κB signaling pathway in cervical cancer cells. Conclusion: MiR-29a-DNMT1-SOCS1 axis plays an important role on invasion and metastasis in cervical cancer via NF-κB signaling pathway.

Keywords: DNMT1; NF-κB; SOCS1; cervical cancer; invasion and metastasis; methylation; miR-29a.

MeSH terms

  • Adult
  • Aged
  • Apoptosis / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation
  • DNA (Cytosine-5-)-Methyltransferase 1 / genetics
  • DNA Methylation*
  • Decitabine / pharmacology
  • Epithelial-Mesenchymal Transition / drug effects
  • Epithelial-Mesenchymal Transition / genetics
  • Female
  • Gene Expression Regulation, Neoplastic* / drug effects
  • Genes, Reporter
  • Humans
  • MicroRNAs / genetics*
  • Middle Aged
  • NF-kappa B / metabolism
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Neoplasm Staging
  • RNA Interference*
  • Suppressor of Cytokine Signaling 1 Protein / genetics*
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / pathology*

Substances

  • MIRN29a microRNA, human
  • MicroRNAs
  • NF-kappa B
  • SOCS1 protein, human
  • Suppressor of Cytokine Signaling 1 Protein
  • Decitabine
  • DNA (Cytosine-5-)-Methyltransferase 1
  • DNMT1 protein, human