Translational control of Bcl-2 promotes apoptosis of gastric carcinoma cells

BMC Cancer. 2021 Jan 5;21(1):12. doi: 10.1186/s12885-020-07711-6.

Abstract

Background: Anti-apoptotic protein Bcl-2 plays a substantial role in the carcinogenesis, whereas the regulation for Bcl-2 in gastric carcinoma (GC) is poorly understood. Specifically, a role of microRNA (miR)-383 in the control of Bcl-2 has not been shown in GC and thus addressed in the current study.

Methods: We investigated the levels of miR-383 and Bcl-2 in 50 GC specimens, and compared them with patients' clinical characteristics. Bioinformatics analyses and luciferase-reporter assay were applied for analyzing the relationship between Bcl-2 and miR-383. An CCK assay was used to determine the survival of Fluorouracil-treated GC cells, and apoptosis of GC cells was assessed by flow cytometric FITC Annexin V apoptosis detection assay and expression of apoptosis-associated proteins.

Results: The levels of miR-383 were lower while the levels of Bcl-2 levels were higher in GC specimens, compared to tissue from the adjacent non-tumor region. Low miR-383 and high Bcl-2 seemed to be associated with high malignancy and metastasis. In GC specimens, the levels of Bcl-2 and miR-383 inversely correlated. The overall survival of miR-383-low cases was poorer. Mechanistically, miR-383 targeted the 3'-UTR of Bcl-2 mRNA to inhibit its protein translation. Overexpression of miR-383 downregulated Bcl-2, resulting in reduced survival of Fluorouracil-treated GC cells. Similar conclusion was drawn through analysis of published database.

Conclusion: MiR-383 reduces survival of Fluorouracil-treated GC cells through downregulating of Bcl-2.

Keywords: Bcl-2; Chemotherapy; Gastric carcinoma (GC); miR-383.

MeSH terms

  • Antimetabolites, Antineoplastic / pharmacology
  • Apoptosis*
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Cell Proliferation
  • Fluorouracil / pharmacology
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Prognosis
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Stomach Neoplasms / drug therapy
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology*
  • Tumor Cells, Cultured

Substances

  • Antimetabolites, Antineoplastic
  • BCL2 protein, human
  • Biomarkers, Tumor
  • MIRN383 microRNA, human
  • MicroRNAs
  • Proto-Oncogene Proteins c-bcl-2
  • Fluorouracil