Conclusion: Our findings not only illustrate a function of Dyrk3 in reprograming HCC metabolism by negatively regulating NCOA3/ATF4 transcription factor complex but also identify NCOA3 as a phosphorylation substrate of Dyrk3, suggesting the Dyrk3/NCOA3/ATF4 axis as a potential candidate for HCC therapy.
Importantly, although expression of SRC-1 and SRC-3 did not reveal any significant differences (30 vs. 40%) in normal liver tissue, HCC and CCC expression of SRC-1 was significantly decreased compared with that of SRC-3 (9.3 vs. 36%, and 6.7 vs. 67.7% for HCC and CCC, respectively).
Increasing evidence suggests that the three homologous members of steroid receptor co-activator (SRC) family (SRC-1, SRC-2, and SRC-3) play key roles in enhancing cell proliferation in various human cancers, such as breast, prostate, and hepatocellular carcinoma.
In addition, MMP-9 expression in AIB1-postive HCC was significantly higher than that in AIB1-negative HCC, suggesting that AIB1-postive HCC may be more invasive.
The current results strongly suggest that amplifications of the c-myc and AIB1 oncogenes are late genetic alterations in the progression of HCC and are correlated with a poor prognosis.