BOP1 Silencing Suppresses Gastric Cancer Proliferation through p53 Modulation

Curr Med Sci. 2021 Apr;41(2):287-296. doi: 10.1007/s11596-021-2345-y. Epub 2021 Apr 20.

Abstract

Block of proliferation 1 (BOP1) is a key protein involved in ribosome maturation and affects cancer progression. However, its role in gastric cancer (GC) remains unknown. This study aimed to explore the expression of BOP1 in GC and its potential mechanisms in regulating GC growth, and the relationship between BOP1 level in cancer tissues and survival was also analyzed. The expression of BOP1 was examined by immunohistochemistry (IHC) in a cohort containing 387 patients with primary GC. Cultured GC cells were treated by siRNA to knock down the BOP1 expression, and examined by CCK-8 assay and plate clone formation to assess cell proliferation in vitro. Apoptotic rate of cultured GC cells was detected by flow cytometry with double staining of AnnxinV/PI. The xenografted mouse model was used to assess GC cell proliferation in vivo. Western blot and IHC were also performed to detect the expression levels of BOP1, p53 and p21. Patients with higher level of BOP1 in cancer tissues had significantly poorer survival. BOP1 silencing significantly suppressed GC cell proliferation both in vitro and in vivo. It blocked cell cycle at G0/G1 phase and led to apoptosis of GC cells via upregulating p53 and p21. BOP1 silencing-induced suppression of cell proliferation was partly reversed by pifithrin-α (a p53 inhibitor). Our study demonstrated that BOP1 up-regulation may be a hallmark of GC and it may regulate proliferation of GC cells by activating p53. BOP1 might be considered a novel biomarker of GC proliferation, and could be a potential indicator of prognosis of GC patients. BOP1 might also be a potential target for the treatment of GC patients if further researched.

Keywords: block of proliferation 1; cell proliferation; gastric cancer; p53K.

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Cell Cycle / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Silencing*
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Middle Aged
  • Multivariate Analysis
  • Prognosis
  • RNA-Binding Proteins / genetics*
  • RNA-Binding Proteins / metabolism
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology*
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • BOP1 protein, human
  • RNA-Binding Proteins
  • Tumor Suppressor Protein p53