A possible connection between adhesion regulating molecule 1 overexpression and nuclear factor kappa B activity in hepatocarcinogenesis

Abstract

Abstract. Adhesion regulating molecule 1 (ADRM1), a 19S proteasome cap-associated protein, and nuclear factor kappa B (NF-κB), a protein transcription factor controlling DNA transcription, may play an important role in tumorigenesis. Overexpression of ADRM1 and activation of NF-κB are wellobserved in hepatocellular carcinoma (HCC). However, little is known about whether both are functionally connected during hepatocarcinogenesis, and the mechanisms involved. In this study, using laboratory techniques including short hairpin RNA (shRNA)-mediated knockdown, immunohistochemistry (IHC), both semi-quantitative and real-time RT-PCR, western blotting, MTT assay, transwell assay, flow cytometry and electrophoretic mobility shift assay (EMSA), the expression of ADRM1, the effects of ADRM1 knockdown on NF-κB activity, as well as the biological behavior of HCC cells including proliferation, migration, invasion and apoptosis were investigated in the samples from HCC patients and HCC cell lines. We found that both mRNA and protein levels of ADRM1 were increased in HCC tissues and that this increase in ADRM1 expression was parallel to the metastatic potential of HCC cell lines. After ADRM1 knockdown in MHCC97-H cells, the expression of IκB-α was increased and the NF-κB activity was reduced. Furthermore, ADRM1 knockdown inhibited MHCC97-H cell proliferation and induced cell apoptosis, and the migration and invasion of MHCC97-H cells were significantly repressed. These results indicate that there is a clear functional connection between ADRM1 and NF-κB in hepatocarcinogenesis, despite the precise mechanisms through which the two work together still being unknown.

Targeting proteasome ubiquitin receptor Rpn13 in multiple myeloma

“…These data are in concert with earlier reports that Rpn13 KD inhibits proliferation and induces apoptosis in hepatocarcinogenesis models. 48 We next used a novel agent RA190 that targets Rpn13. 25 The specificity of Rpn13 inhibitor RA190 was confirmed using multiple strategies: first, assays using CRISPR/Cas9 Rpn13-KO cells shows that loss of Rpn13 triggers cell death; conversely, rescue experiments with Rpn13-WT in Rpn13-KO cells restores sensitivity to RA190; second, RA190 impaired cellular protein degradation, assessed using a reporter cell line expressing Ub-tagged GFPu-1 and polyubiquitylation; third, RA190 blocks proteasome function without inhibiting the 20S proteasomal activities; and fourth, studies using both cellular extracts and recombinant proteins to assess DUB activity show that RA190 does not inhibit 19S-associated DUB activity.…”

High Concentrations of Atmospheric Ammonia Induce Alterations in the Hepatic Proteome of Broilers (Gallus gallus): An iTRAQ-Based Quantitative Proteomic Analysis

“…MCMBP is known to be crucial for DNA replication, regulating initiation and elongation of DNA and providing DNA helicase activity [ 39 ]. ADRM1 is an integral plasma membrane protein that promotes cell adhesion, which has been shown to be induced in hepatocellular carcinoma (HCC) [ 40 ]. NOP58 (NOP58 ribonucleoprotein) is essential for ribosomal biogenesis, whereas an increased expression of this protein was observed in hyperglycemia-induced vascular injury [ 41 , 42 ].…”

Network Biomarkers of Bladder Cancer Based on a Genome-Wide Genetic and Epigenetic Network Derived from Next-Generation Sequencing Data

“…In Figure 3 , our results reveal that ADRM1 regulates KPNA2, which promotes proliferation, and is mediated by the aging-related proteins, HSP90B1, CALR, HSPA5, PDIA3, RPN1, and ECT2, the smoking-related proteins, HUWE1, HSPA5, and ECT2, and the epigenetic regulation of ENO1, HSP90B1, CALR, and PDIA3, through the SUP and ER signaling pathways. ADRM1 knockdown leads to a reduction of cancer cell proliferation and has been found in gastric [ 37 ], ovarian [ 38 ], liver [ 39 ], and colorectal cancers [ 40 ] and acute leukemia [ 41 ]. Therefore, the results support the hypothesis that aging is the most important factor in inducing bladder carcinogenesis through the SUP pathway.…”