BCL11A Facilitates Cell Proliferation and Metastasis in Neuroblastoma via Regulating the PI3K/Akt Signaling Pathway

Curr Cancer Drug Targets. 2022;22(11):919-930. doi: 10.2174/1568009622666220728123748.

Abstract

Purpose: The study aims to access the value of B-cell lymphoma/leukemia 11A (BCL11A) in the prognosis of patients with neuroblastoma (NB) and to explore its role and possible mechanism in NB.

Methods: Tumor specimens from 53 children with neuroblastoma were evaluated for the relationship between BCL11A expression level and prognosis of NB patients. Online datasets like SEQC and Asgharzadeh were analyzed to further check out the suppose.The role of BCL11A in the proliferation and migration of NB cells was studied by functional experiments such as CCK8, colony formation, flow cytometry, transwell and wound healing assay after knocking down BCL11A by small interfering RNA (siRNA) in vitro. The protein makers of the potential pathways were tested by western blot.

Results: High expression of BCL11A in NB patients was closely correlated with high-risk and poor prognosis. The proliferation and migration abilities of NB cell lines SK-N-BE(2) and IMR-32 were significantly impaired by silencing BCL11A. Downregulation of BCL11A expression level in NB cells inhibited the epithelial-mesenchymal transition (EMT) process and affected the PI3K/Akt signaling pathway.

Conclusion: As a prognostic indicator of survival in NB patients, BCL11A might serve as a potential therapeutic target. BCL11A played a regulatory role in cell proliferation, invasion, and migration in NB, which may be through the PI3K/AKT signaling pathway and induce EMT.

Keywords: BCL11A; Neuroblastoma; invasion; metastasis; prognosis; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation
  • Child
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Neoplastic Processes
  • Neuroblastoma* / metabolism
  • Neuroblastoma* / pathology
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Small Interfering
  • Repressor Proteins* / metabolism
  • Signal Transduction*
  • Transcription Factors / metabolism

Substances

  • BCL11A protein, human
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • Repressor Proteins
  • RNA, Small Interfering
  • Transcription Factors