Molecular Mechanism of Circ_0088300-BOLL Interaction Regulating Mitochondrial Metabolic Reprogramming and Involved in Gastric Cancer Growth and Metastasis

J Proteome Res. 2023 Dec 1;22(12):3793-3810. doi: 10.1021/acs.jproteome.3c00476. Epub 2023 Nov 12.

Abstract

This study aims to investigate the effect and molecular mechanism of the interaction between circRNA circ_0088300 and the RNA binding protein (RBP) BOLL on the growth and metastasis of gastric cancer. A prognostic risk model was established by screening differentially expressed RBP genes from the TCGA database, and BOLL was identified as a critical RBP. Gene Set Enrichment analysis (GSEA) showed that BOLL was associated with mitochondrial function. The upregulation fold change of circ_0088300 was the highest in the GSE93541 data set, and the RPISeq database confirmed its binding relationship with BOLL. In vitro experiments showed that BOLL regulates mitochondrial metabolism and cancer cell function and circ_0088300 upregulates the expression level of BOLL. In vivo experiments demonstrated that knocking down circ_0088300 can inhibit tumor growth and metastasis, whereas overexpression of BOLL can reverse this effect. In conclusion, we have reached a preliminary conclusion that upregulation of BOLL by circ_0088300 promotes gastric cancer growth and metastasis by promoting mitochondrial metabolic reprogramming.

Keywords: BOLL; RNA-binding protein; circ_0088300; circular RNA; epithelial−mesenchymal transition (EMT); gastric cancer; mitochondrial metabolic reprogramming.

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs* / genetics
  • RNA, Circular / genetics
  • RNA, Circular / metabolism
  • Stomach Neoplasms* / metabolism
  • Up-Regulation

Substances

  • MicroRNAs
  • RNA, Circular