CAPG facilitates diffuse large B-cell lymphoma cell progression through PI3K/AKT signaling pathway

Hum Immunol. 2022 Dec;83(12):832-842. doi: 10.1016/j.humimm.2022.10.001. Epub 2022 Oct 14.

Abstract

Objective: Diffuse large B-cell lymphoma (DLBCL) is a genetically heterogeneous tumor. Currently, macrophage-capping protein (CAPG) has been discovered to play a crucial part as a regulator in various cancers. However, it still remains unclear regarding its regulatory mechanism in DLBCL. Therefore, this study focused on revealing the mechanism underlying CAPG in DLBCL.

Methods: The bioinformatics analysis was conducted to predict the expression of CAPG in DLBCL and its downstream target genes. qRT-PCR was utilized to detect mRNA expression levels of CAPG and CEBPA. Western blot was performed to examine the expression levels of related proteins. Then we employed flow cytometry for the analysis of cell cycle and apoptosis. We also used MTT assay to measure cell survival and IHC assay to detect CAPG expression in DLBLC tissues. Then, ChIP was used to determine the binding of CEBPA and CAPG. For in vivo experiments, xenograft models were employed to investigate the effect of CAPG on DLBCL.

Results: High-level of CAPG expression was found in DLBCL cells and tissues. CAPG could strengthen the proliferative and invasive abilities of DLBCL cells, inhibit cell apoptosis, and activate PI3K/AKT signaling pathway. CAPG overexpression accelerated malignant progression of DLBCL cells. In addition, CAPG expression was regulated by CEBPA.

Conclusion: CAPG enhances the proliferation and invasion of DLBCL cells by promoting PI3K/AKT signaling pathway, which is expected to be a promising target for DLBCL.

Keywords: Apoptosis; CAPG; DLBCL; Invasion; Proliferation.

MeSH terms

  • Animals
  • Apoptosis
  • Cell Line, Tumor
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lymphoma, Large B-Cell, Diffuse* / genetics
  • Microfilament Proteins / metabolism
  • Nuclear Proteins / genetics
  • Phosphatidylinositol 3-Kinases* / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction / genetics

Substances

  • CAPG protein, human
  • Microfilament Proteins
  • Nuclear Proteins
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt