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.

Expression of possible targets for new proteasome inhibitors in diffuse large B‐cell lymphoma

“…Adhesion regulating molecule 1 (ADRM1) is a polyubiquitin receptor on the 26S proteasome. ADRM1 has been found to be upregulated in many cancers and in acute leukaemia . The strong expression of ADRM1 in this study is in concordance with those findings.…”

“…Indeed, drugs targeting DUBs are under development for many different cancer types, for example lymphoma . Furthermore, adhesion regulating molecule 1 (ADRM‐1), a receptor of the 26S proteasome subunit, has been shown to be upregulated in many solid cancers and in acute leukaemia, but its expression in lymphoma has so far not been studied .…”

Is ADRM1 a Good Target for Cancer Therapy?

“…IκB-α, a protein that binds to NF-κB and inhibits its nuclear translocation, is one of the substrates of the ADRM1/UCH37 complex. The study by Zheng et al [3 ]in this issue of Acta Haematologica further confirms the mechanism by elegantly demonstrating increased nuclear fraction of p65, one of the NF-κB proteins, in the presence of overexpressed ADRM1. Inhibiting ADRM1 has also been shown to downregulate the growth factor GIPC1 and upregulate the tumor suppressors RECK and p53 [4,5].…”

The Proteasome Ubiquitin Receptor hRpn13 and Its Interacting Deubiquitinating Enzyme Uch37 Are Required for Proper Cell Cycle Progression

“…The gene expressing hRpn13 is amplified in ovarian (42), colorectal (43), acute leukemia (44), and metastatic gastric cancers (45), with the latter study implicating hRpn13 as promoting gastric epithelial cell proliferation. High levels of Uch37 have been found in lung, breast, ovarian, vulva, and parathyroid cancers (reviewed in Ref.…”