Serum anti-Ku86 is a potential biomarker for early detection of hepatitis C virus-related hepatocellular carcinoma

Nomura, Fumio; Sogawa, Kazuyuki; Noda, Kenta; Seimiya, Masanori; Matsushita, Hiroshi; Miura, Taro; Tomonaga, Takeshi; Yoshitomi, Hideyuki; Imazeki, Fumio; Takizawa, Hirotaka; Mogushi, Kaoru; Miyazaki, Masaru; Yokosuka, Osamu

doi:10.1016/j.bbrc.2012.04.099

Cited by 31 publications

(24 citation statements)

References 29 publications

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“…Ku86, the 86-kDa subunit of Ku encoded by human XRCC5, is a critical factor in the NHEJ DNA repair pathway [37]. Ku86 is overexpressed in HCC tissues and anti-Ku86/Ku70 autoantibodies in patient serum are a candidate biomarker for detecting early-stage hepatitis C virus-related HCC [27,38]. Previous studies also suggested that Ku86 variants may play a role in determining HCC susceptibility [39].…”

Section: Discussionmentioning

confidence: 99%

Alternative splicing of FBP-interacting repressor coordinates c-Myc, P27Kip1/cyclinE and Ku86/XRCC5 expression as a molecular sensor for bleomycin-induced DNA damage pathway

et al. 2013

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The far-upstream element-binding protein-interacting repressor (FIR) is a c-myc transcriptional suppressor. FIR is alternatively spliced to lack the transcriptional repression domain within exon 2 (FIRΔexon2) in colorectal cancers. FIR and FIRΔexon2 form homo- or heterodimers that complex with SAP155. SAP155, a subunit of the essential splicing factor 3b subcomplex in the spliceosome, is required for proper P27Kip1 pre-mRNA splicing, and P27Kip1 arrests cells at G1. In contrast, FIR was co-immunoprecipitated with Ku86 and DNA-PKcs. siRNA against Ku86/Ku70 decreased FIR and P27Kip1 expression, whereas siRNA against FIR decreased Ku86/XRCC5 and P27Kip1 expression. Thus the mechanical interaction of FIR/FIRΔexon2/SAP155 bridges c-myc and P27Kip1 expression, potentially integrates cell-cycle progression and c-myc transcription in cell.Bleomycin (BLM) is an anticancer agent that introduces DNA breaks. Because DNA breaks generate the recruitment of Ku86/Ku70 to bind to the broken DNA ends, the possible involvement of FIR and Ku86/Ku70 interaction in the BLM-induced DNA damage repair response was investigated in this study. First, BLM treatment reduced SAP155 expression and increased FIR and FIRΔexon2 mRNA expression as well as the ratio of FIRΔexon2:FIR in hepatoblastoma cells (HLE and HLF). Second, FIR or FIRΔexon2 adenovirus vectors (Ad-FIR or Ad-FIRΔexon2) increased Ku86/Ku70 and P27Kip1 expression in vitro. Third, BLM decreased P27Kip1 protein expression, whereas increased P27Kip1 and γH2AX expression with Ad-FIRΔexon2. Together, the interaction of FIR/SAP155 modulates FIR splicing and involves in cell-cycle control or cell fate via P27Kip1 and c-myc in BLM-induced DNA damage pathway. This novel function of FIR splicing will contribute to clinical studies of cancer management through elucidating the mechanical interaction of FIR/FIRΔexon2/SAP155 as a potential target for cancer treatment.

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Section: Discussionmentioning

confidence: 99%

Alternative splicing of FBP-interacting repressor coordinates c-Myc, P27Kip1/cyclinE and Ku86/XRCC5 expression as a molecular sensor for bleomycin-induced DNA damage pathway

et al. 2013

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“…In contrast, there are no data available, to our knowledge that associates autoantibodies against p53 with patients' clinical characteristics. In patients with colorectal cancer (CRC), there is an increase in the prevalence of anti-p53 autoantibodies in carcinoma in-situ (6%) compared with adenomas (1%), indicating that the level of anti-p53 autoantibody increases with CRC [36] hnRNP L Akada et al [42] HSP70, SOD2, and PRDX6 Shao et al [41] Glucose-regulated protein 78 Nomura et al [39] Ku86 Liu et al [40] CENPF, DDX3, HSPA4, HSPA5, VIM, LMNB1, and p53 Pekáriková et al [21] CRT Chen et al [28] Sui1, RalA Wang et al [43] KRT23, AHSG and FTL Wang et al [44] RalA Looi et al [45] HSP60, HSP70 Li et al [35] DDX3, eEF2, AIF, hnRNP A2, PBP, and TIM Chen et al [46] EIF3SI, LDHA, RFC2, and MCART1 Zhang et al [27] IMP1, IMP2, IMP3, p53, c-myc, cyclin B1, survivin and p16 Akere et al [13] p53 Zhou et al [47] HCC-22-5 Takashima et al [48] HSP70, GAPDH, PRX, Mn-SOD Looi et al [49] p16 Yagihashi et al [25] Survivin Su et al [17] IMP2 Himoto et al [19] IMPs Himoto et al [18] IMPs, p53, c-myc, and survivin Zhang et al [24] c-myc, cyclin B1, IMP1, Koc, p53, IMP2, and survivin Soo Hoo et al [50] p53, IMP2, Koc, CENP-F, p90 Le Naour et al [51] CRT, CK8, NDK-A, and ATP5B Zhang et al [23] IMP2, CENPF Zhang et al [20] IMP2 Raedle et al [52] p53 Covini et al [22] Cyclin B1 Imai et al [53] HCC1 TAAs: Tumor-associated antigens; HCC: Hepatocellular carcinoma; IMP: Insulin-like growth factor mRNA-binding; CENPF: Centromere protein F. 9…”

Section: Association Of the Prevalence Of Autoantibodies With The CLImentioning

confidence: 99%

“…However, their value for this purpose is controversial. There is concern that there is no single anti-TAA autoantibody with high sensitivity and specificity that detects HCC, and no large-scale clinical trial has been conducted to validate candidate TAAs [26,28,35,[39][40][41] . Further studies of large populations with precise clinical information should be conducted to determine whether autoantibodies to TAAs are associated with patients' clinical characteristics as well studies on the mechanism of the production of TAAs, with the aim of clarifying the role of specific TAAs as biomarkers for the early diagnosis and prognosis of HCC.…”

Section: Prospectsmentioning

confidence: 99%

Autoantibodies against tumor-associated antigens for detection of hepatocellular carcinoma

Huang

2015

WJH

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Hepatocellular carcinoma (HCC) is one of the most common tumors worldwide. The survival rate after the onset of symptoms is generally less than one year for the late presentation of HCC, and reliable tools for early diagnosis are lacking. Therefore, novel biomarkers for the early detection of HCC are urgently required. Recent studies show that the abnormal release of proteins by tumor cells can elicit humoral immune responses to self-antigens called tumor-associated antigens (TAAs). The corresponding autoantibodies can be detected before the clinical diagnosis of cancer. Therefore, there is growing interest in using serum autoantibodies as cancer biomarkers. In this review, we focus on the advances in research on autoantibodies against TAAs as serum biomarker for detection of HCC, the mechanism of the production of TAAs, and the association of autoantibodies with patients' clinical characteristics.

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“…Recently, glucose-regulated protein 78 (GRP78), which is a chaperone protein belonging to the HSP70 family, was captured as a novel TAA in patients with HCC [32]. Fatty acid synthase was also identified as a novel TAA from those patients [39].…”

Section: ) Diagnostic Significance Of Anti-taasmentioning

confidence: 99%

Relationship between Autoimmunity and Cancer or Metabolic Abnormality in Liver Diseases

Himoto¹,

Nishioka²,

Masaki³

2014

TOAUTOJ

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Recent advances in the serological analysis of recombinant cDNA expression libraries and proteomic analysis have enabled the identification of numerous kinds of novel autoantigens, especially tumor-associated antigens (TAAs). The emergence of antibodies to TAAs might imply that an autoimmune response was involved in the malignant transformation. These autoantibodies to TAAs often have predictive value as well as diagnostic relevance. Similarly, the relationship between autoimmunity and metabolic abnormalities, including insulin resistance and hepatic steatosis, has been also documented. Metabolic abnormalities are frequently associated with autoimmune diseases. In contrast, autoimmune reactions were occasionally involved in the process of metabolic dysregulation. This review primarily focuses on the current trends for the relationship between autoimmunity and cancer or metabolic abnormalities in liver disease and the current interpretations of autoantibodies in those diseases.

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Serum anti-Ku86 is a potential biomarker for early detection of hepatitis C virus-related hepatocellular carcinoma

Cited by 31 publications

References 29 publications

Alternative splicing of FBP-interacting repressor coordinates c-Myc, P27Kip1/cyclinE and Ku86/XRCC5 expression as a molecular sensor for bleomycin-induced DNA damage pathway

Alternative splicing of FBP-interacting repressor coordinates c-Myc, P27Kip1/cyclinE and Ku86/XRCC5 expression as a molecular sensor for bleomycin-induced DNA damage pathway

Autoantibodies against tumor-associated antigens for detection of hepatocellular carcinoma

Relationship between Autoimmunity and Cancer or Metabolic Abnormality in Liver Diseases

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