Erb‑B2 Receptor Tyrosine Kinase 2 is negatively regulated by the p53‑responsive microRNA‑3184‑5p in cervical cancer cells

Oncol Rep. 2021 Jan;45(1):95-106. doi: 10.3892/or.2020.7862. Epub 2020 Nov 19.

Abstract

The oncogenic role of Erb‑B2 Receptor Tyrosine Kinase 2 (ERBB2) has been identified in several types of cancer, but less is known on its function and mechanism of action in cervical cancer cells. The present study employed a multipronged approach to investigate the role of ERBB2 in cervical cancer. ERBB2 and microRNA (miR)‑3184‑5p expression was assessed in patient‑derived cervical cancer biopsy tissues, revealing that higher levels of ERBB2 and lower levels of miR‑3184‑5p were associated with clinicopathological indicators of cervical cancer progression. Furthermore, ERBB2 stimulated proliferation, migration and sphere‑formation of cervical cancer cells in vitro. This effect was mediated by enhanced phosphatidylinositol‑4,5‑bisphosphate 3‑kinase catalytic subunit α activity. Additionally, it was revealed that miR‑3184‑5p directly suppressed ERBB2 in cervical cancer cells. The p53 activator Mithramycin A stimulated p53 and miR‑3184‑5p expression, thereby lowering the levels of ERBB2 and attenuating proliferation, migration and sphere‑formation of cervical cancer cells. In conclusion, the findings of the present study suggested ERBB2 as an oncogenic protein that may promote invasiveness in cervical cancer cells. Treatment of cervical cancer cells with the p53 activator Mithramycin A restored the levels of the endogenous ERBB2 inhibitor miR‑3184‑5p and may represent a novel treatment strategy for cervical cancer.

Keywords: cervical cancer; Erb‑B2 Receptor Tyrosine Kinase 2; microRNA‑3184‑5p; p53.

Publication types

  • Observational Study

MeSH terms

  • Adult
  • Aged
  • Biopsy
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Movement / genetics
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics
  • Cervix Uteri / pathology
  • Cervix Uteri / surgery
  • Class I Phosphatidylinositol 3-Kinases / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Hysterectomy
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Neoplasm Invasiveness
  • Plicamycin / analogs & derivatives
  • Plicamycin / pharmacology
  • Receptor, ErbB-2 / genetics*
  • Tumor Suppressor Protein p53 / agonists
  • Tumor Suppressor Protein p53 / metabolism*
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / surgery

Substances

  • MIRN3184 microRNA, human
  • MicroRNAs
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • mithramycin A
  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CA protein, human
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Plicamycin