Regulation of lymphoma in vitro by CLP36 through the PI3K/AKT/CREB signaling pathway

PeerJ. 2024 Dec 24:12:e18693. doi: 10.7717/peerj.18693. eCollection 2024.

Abstract

Background: CLP36 is also known as PDZ and LIM Domain 1 (PDLIM1) that is a ubiquitously-expressed α-actinin-binding cytoskeletal protein involved in carcinogenesis, and our current study aims to explore its involvement in lymphoma.

Methods: Accordingly, the CLP36 expression pattern in lymphoma and its association with the overall survival was predicted. Then, qPCR was applied to gauge CLP36 expression in lymphoma cells and determine the knockdown efficiency. The survival, proliferation and apoptosis of CLP36-silencing lymphoma cells were tested. Cell viability, proliferation and apoptosis were assessed based on cell counting kit-8 (CCK-8) assay, colony formation assay, EdU staining, and flow cytometry, respectively. Additionally, qPCR was used to calculate the expressions of proteins associated with metastasis and apoptosis, while immunoblotting was employed to determine the phosphorylation status of phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/cAMP-response element binding protein (CREB).

Results: CLP36 expression was relatively higher in lymphoma, which was associated with a poor prognosis. Also, CLP36 was highly-expressed in lymphoma cells and the silencing of CLP36 contributed to the suppressed survival and proliferation as well as the enhanced apoptosis of lymphoma cells. Further, CLP36 silencing repressed the expressions of Cadherin 2 (CDH2) and Vimentin (VIM) yet promoted those of Bax and Caspase 3 in lymphoma cells, concurrent with the reduction on the phosphorylation of PI3K, AKT and CREB, all of which were confirmed to be positively correlated with CLP36.

Conclusion: This study, so far as we are concerned, provided evidence on the involvement of CLP36/PI3K/AKT/CREB axis in lymphoma, which may be contributive for the identification on the relevant molecular targets of lymphoma.

Keywords: CLP36; Lymphoma; PI3K/AKT/CREB; Proliferation; Survival.

MeSH terms

  • Apoptosis*
  • Cell Line, Tumor
  • Cell Proliferation*
  • Cell Survival
  • Cyclic AMP Response Element-Binding Protein* / genetics
  • Cyclic AMP Response Element-Binding Protein* / metabolism
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • LIM Domain Proteins* / genetics
  • LIM Domain Proteins* / metabolism
  • Lymphoma* / genetics
  • Lymphoma* / metabolism
  • Lymphoma* / pathology
  • Phosphatidylinositol 3-Kinases* / metabolism
  • Proto-Oncogene Proteins c-akt* / metabolism
  • Signal Transduction*

Substances

  • Proto-Oncogene Proteins c-akt
  • Cyclic AMP Response Element-Binding Protein
  • LIM Domain Proteins
  • Phosphatidylinositol 3-Kinases
  • CREB1 protein, human
  • Cytoskeletal Proteins

Grants and funding

The authors received no funding for this work.