DEPDC1B enhances malignant phenotypes of multiple myeloma through upregulating CCNB1 and inhibiting p53 signaling pathway

Tissue Cell. 2024 Feb:86:102263. doi: 10.1016/j.tice.2023.102263. Epub 2023 Nov 4.

Abstract

The identification and investigation of key molecules involved in the pathogenesis of multiple myeloma (MM) hold paramount clinical significance. This study primarily focuses on elucidating the role of DEPDC1B within the context of MM. Our findings robustly affirm the abundant expression of DEPDC1B in MM tissues and cell lines. Notably, DEPDC1B depletion exerted inhibitory effects on MM cell proliferation and migration while concurrently facilitating apoptosis and G2 cell cycle arrest. These outcomes stand in stark contrast to the consequences of DEPDC1B overexpression. Furthermore, we identified CCNB1 as a putative downstream target, characterized by a co-expression pattern with DEPDC1B, mediating DEPDC1B's regulatory influence on MM. Additionally, our results suggest that DEPDC1B knockdown may activate the p53 pathway, thereby impeding MM progression. To corroborate these in vitro findings, we conducted in vivo experiments that further validate the regulatory role of DEPDC1B in MM and its interaction with CCNB1 and the p53 pathway. Collectively, our research underscores DEPDC1B as a potent promoter in the development of MM, representing a promising therapeutic target for MM treatment. This discovery bears significant implications for future investigations in this field.

Keywords: Cell proliferation; DEPDC1B; Molecular mechanism; Multiple myeloma; P53 signaling pathway.

MeSH terms

  • Apoptosis / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Cyclin B1 / genetics
  • Cyclin B1 / metabolism
  • Cyclin B1 / pharmacology
  • GTPase-Activating Proteins / metabolism
  • Humans
  • Multiple Myeloma* / metabolism
  • Signal Transduction / genetics
  • Tumor Suppressor Protein p53* / genetics
  • Tumor Suppressor Protein p53* / metabolism

Substances

  • Tumor Suppressor Protein p53
  • CCNB1 protein, human
  • Cyclin B1
  • DEPDC1B protein, human
  • GTPase-Activating Proteins