Knockdown of Adhesion-Regulating Molecule 1 Inhibits Proliferation in HL60 Cells

Acta Haematol. 2015;134(2):88-100. doi: 10.1159/000369916. Epub 2015 Apr 21.

Abstract

Background/aims: Adhesion-regulating molecule 1 (ADRM1), a receptor located on the 26S proteasome, is upregulated in many solid cancers. However, little is known about its role in acute leukemia (AL).

Methods: We determined ADRM1 expression levels in both untreated AL samples and leukemia cell lines using real-time polymerase chain reaction or Western blot analysis. Growth curves, colony formation assays, cell cycle and apoptosis analyses, cell migration and invasion assays and NF-κB p65 nuclear translocation assays via Western blotting were used to examine the biological behavior of HL60 cells and the underlying mechanism.

Results: ADRM1 was upregulated in both untreated AL samples and leukemia cell lines. ADRM1 knockdown significantly suppressed HL60 cell proliferation (48.82 ± 12.58%) and colony formation and caused cell cycle arrest in the G0/G1 phase. Furthermore, we confirmed that ADRM1 knockdown suppressed p65 nuclear translocation.

Conclusion: Our study revealed that ADRM1 was overexpressed in AL, especially in CD34+ leukemia stem and progenitor cells. ADRM1 may play a role in AL via the proteasome-ubiquitin pathway by potentially sustaining the activation of NF-κB signaling.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD34 / metabolism
  • Apoptosis
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • G1 Phase
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • HL-60 Cells
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Leukemia / blood
  • Leukemia / metabolism
  • Leukemia / pathology
  • Leukemia / therapy
  • Leukemia, Promyelocytic, Acute / blood
  • Leukemia, Promyelocytic, Acute / metabolism*
  • Leukemia, Promyelocytic, Acute / pathology
  • Leukemia, Promyelocytic, Acute / therapy
  • Leukocytes, Mononuclear / metabolism
  • Leukocytes, Mononuclear / pathology
  • Membrane Glycoproteins / antagonists & inhibitors*
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • Neoplasm Proteins / antagonists & inhibitors*
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • RNA Interference*
  • RNA, Small Interfering
  • Resting Phase, Cell Cycle
  • Tumor Cells, Cultured
  • Tumor Stem Cell Assay

Substances

  • ADRM1 protein, human
  • Antigens, CD34
  • Intracellular Signaling Peptides and Proteins
  • Membrane Glycoproteins
  • Neoplasm Proteins
  • RNA, Small Interfering