BMI‑1 promotes invasion and metastasis in endometrial adenocarcinoma and is a poor prognostic factor

Oncol Rep. 2020 May;43(5):1630-1640. doi: 10.3892/or.2020.7539. Epub 2020 Mar 10.

Abstract

Endometrial adenocarcinoma is one of the most common types of gynecological malignancies and its incidence and mortality rates are increasing. Due to tumor recurrence and metastasis, the overall five‑year survival rate of patients with endometrial adenocarcinoma is shortened. The aim of the present was to investigate the role of the polycomb group protein B‑lymphoma Mo‑MLV insertion region 1 (BMI‑1) in the invasion, metastasis and the epithelial‑mesenchymal transition (EMT) of endometrial adenocarcinoma cells, as well its effects on the prognosis of patients with endometrial adenocarcinoma. Immunohistochemistry was used to examine the expression profile of BMI‑1 in normal and endometrial adenocarcinoma tissues. Western blotting was used to examine the expression levels of BMI‑1 and EMT markers. Kaplan‑Meier plots and a Cox proportional hazards model were used to assess the overall survival. MTT cell viability assays were used to detect the proliferation of endometrial cancer cells. Transwell assays were used to examine cell migration and invasion. Small interfering RNA was used to downregulate BMI‑1 expression levels, to study its effect on EMT. Immunohistochemical and clinicopathological analyses showed that BMI‑1 expression was increased in endometrial adenocarcinoma tissue compared with the normal endometrial tissue (P<0.05). The increased expression levels of BMI‑1 were closely associated with stage, myometrial invasion and lymph node metastasis (P<0.05). Kaplan‑Meier plots and a Cox proportional hazards model showed that increased BMI‑1 expression was associated with a less favorable prognosis [P=0.040, hazards ratio (HR)=1.596] and was associated with late‑stage adenocarcinoma (P=0.006, HR=1.670). Myometrial invasion (P=0.006, HR=1.509) and lymph node metastasis (P=0.004, HR=1.703) were determined to predict a less favorable prognosis. Downregulation of BMI‑1 reduced migration and invasion in endometrial cancer cells in vivo. It was also found that downregulation of BMI‑1 increased the expression levels of the epithelial markers E‑cadherin and keratin, and decreased the expression levels of the mesenchymal markers N‑cadherin, vimentin and the downstream transcription factor, Slug. In conclusion, BMI‑1 expression was correlated with tumor invasion and metastasis, contributing to deep myometrial invasion and lymph node metastasis, and was a poor prognostic factor for endometrial adenocarcinoma.

Keywords: B-lymphoma Mo-MLV insertion region 1; endometrial adenocarcinoma; clinicopathological parameters; epithelial-mesenchymal transition.

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology*
  • Adult
  • Aged
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Case-Control Studies
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Endometrial Neoplasms / genetics
  • Endometrial Neoplasms / metabolism
  • Endometrial Neoplasms / pathology*
  • Epithelial-Mesenchymal Transition
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lymphatic Metastasis
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Polycomb Repressive Complex 1 / genetics*
  • Polycomb Repressive Complex 1 / metabolism*
  • Prognosis
  • RNA, Small Interfering / pharmacology
  • Up-Regulation*

Substances

  • BMI1 protein, human
  • Biomarkers, Tumor
  • RNA, Small Interfering
  • Polycomb Repressive Complex 1