title: A possible connection between adhesion regulating molecule 1 overexpression             and nuclear factor kappa B activity in hepatocarcinogenesis.
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 well-observed 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.
authors.affiliation: Department of General Surgery, the Second Xiangya Hospital, Central South University, Changsha, Hunan Province 410011, PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Yang
authors.forename: Xiongying
authors.initials: X
authors.lastname: Miao
authors.forename: Yu
authors.initials: Y
authors.lastname: Wen
authors.forename: Jixiong
authors.initials: J
authors.lastname: Hu
authors.forename: Weidong
authors.initials: W
authors.lastname: Dai
authors.forename: Bangliang
authors.initials: B
authors.lastname: Yin
mesh_terms: D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D034622:RNA Interference; D014158:Transcription, Genetic; D015854:Up-Regulation
chemical_list: C500781:ADRM1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D016328:NF-kappa B