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

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.

• Authors: Xiaohui Zheng, Yafei Guo, Yingying Chen, Meilin Chen, Zhenxin Lin, Yong Wu, Yuanzhong Chen
• Journal: Acta haematologica (Acta Haematol) Vol. 134 Issue 2 Pg. 88-100 ( 2015) ISSN: 1421-9662 [Electronic] Switzerland
• PMID: 25896055 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 S. Karger AG, Basel.

Chemical References

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

Topics

• 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, metabolism, pathology, therapy)
• Leukemia, Promyelocytic, Acute (blood, metabolism, pathology, therapy)
• Leukocytes, Mononuclear (metabolism, pathology)
• Membrane Glycoproteins (antagonists & inhibitors, genetics, metabolism)
• Neoplasm Proteins (antagonists & inhibitors, genetics, metabolism)
• RNA Interference
• RNA, Small Interfering
• Resting Phase, Cell Cycle
• Tumor Cells, Cultured
• Tumor Stem Cell Assay