Abstract
BackgroundRecently, it is reported that asparagine synthetase (ASNS) is an independent predictor of surgical survival in hepatocellular carcinoma (HCC) patients. It is also reported that activating transcription factor 6 (ATF6) expression is decreased in HCC patients. So in the present study, we explored the relationship between ASNS and ATF6, and whether ASNS expression was associated with HCC.MethodsATF6 was over expressed in 3 HCC cell lines (HepG2, HepG2.2.15 and SMMC-7721). We then examined the mRNA levels of ASNS and ATF6 in 90 HCC patients, 77 chronic hepatitis B patients and 70 controls. We also genotyped 2 functional polymorphisms in ASNS in a case–control study.ResultsThe expression of ASNS was significantly elevated when ATF6 was over expressed. The expressions of these 2 genes were both decreased in HCC patients, and it was more significantly with ASNS. The mRNA levels of ASNS and ATF6 were positively correlated with each other. rs34050735 was associated with HCC in the case–control study (P = 0.003) and also an independent predictor of overall survival of HCC patients (P = 0.001).ConclusionsTaken together, these findings indicated that rs34050735 in ASNS may associate with HCC and may be a promising biomarker of HCC.
Highlights
It is reported that asparagine synthetase (ASNS) is an independent predictor of surgical survival in hepatocellular carcinoma (HCC) patients
The result showed that when activating transcription factor 6 (ATF6) was over expressed, the mRNA level of ASNS was elevated by 1.86-fold, 1.95-fold and 1.65-fold in HepG2, HepG2.2.15, and SMMC-7721 cells, respectively (P < 0.001) (Fig. 1)
The result showed that nonHBV controls and chronic hepatitis B (CHB) patients had 2.67-fold and 2.08-fold higher ATF6 mRNA levels than HCC patients (P = 5.38E-79), and 2.78-fold and 2.16-fold higher ASNS mRNA levels than HCC patients (P = 9.05E-82)
Summary
It is reported that asparagine synthetase (ASNS) is an independent predictor of surgical survival in hepatocellular carcinoma (HCC) patients. It is reported that activating transcription factor 6 (ATF6) expression is decreased in HCC patients. In the present study, we explored the relationship between ASNS and ATF6, and whether ASNS expression was associated with HCC. Zhang et al reported that asparagine synthetase (ASNS) was an independent predictor of surgical survival and a potential therapeutic target in HCC [2]. The ATF6 gene encodes a transcription factor, acting as an unfolded protein response (UPR) transcriptional activator which regulates gene expression of endoplasmic reticulum (ER) chaperones, ER-associated proteins, and apoptotic genes [9, 10]. We speculated that ATF6 may regulate the expression of ASNS, and ASNA may associated with HCC tumorigenesis. We carried out the present study to test this hypothesis
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