RNA-seq analysis reveals candidate genes associated with proliferation, invasion, and migration in BCL11A knockdown B-NHL cell lines

Ann Hematol. 2023 Jul;102(7):1845-1856. doi: 10.1007/s00277-023-05247-w. Epub 2023 May 6.

Abstract

B-cell lymphoma/leukemia 11A (BCL11A) is highly expressed in B-cell non-Hodgkin lymphoma (B-NHL), blocks cell differentiation, and inhibits cell apoptosis. However, little is known about BCL11A in the proliferation, invasion, and migration of B-NHL cells. Here, we found increased expression of BCL11A in B-NHL patients and cell lines. Knockdown of BCL11A suppressed the proliferation, invasion, and migration of B-NHL cells in vitro and reduced tumor growth in vivo. RNA sequencing (RNA-seq) and KEGG pathway analysis demonstrated that BCL11A-targeted genes were significantly enriched in the PI3K/AKT signaling pathway, focal adhesion, and extracellular matrix (ECM)-receptor interaction (including COL4A1, COL4A2, FN1, SPP1), and SPP1 was the most significantly downregulated gene. qRT‒PCR, western blotting, and immunohistochemistry revealed that silencing BCL11A reduced the expression level of SPP1 in Raji cells. Our study suggested that high level of BCL11A may promote B-NHL proliferation, invasion, and migration, and the BCL11A-SPP1 regulatory axis may play an important role in Burkitt's lymphoma.

Keywords: B-NHL; BCL11A; Metastasis; Proliferation; SPP1.

MeSH terms

  • Apoptosis
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lymphoma, B-Cell*
  • Phosphatidylinositol 3-Kinases* / metabolism
  • Repressor Proteins / metabolism
  • Sequence Analysis, RNA
  • Transcription Factors / metabolism

Substances

  • Phosphatidylinositol 3-Kinases
  • Transcription Factors
  • BCL11A protein, human
  • Repressor Proteins