Abstract
Hepatocellular carcinoma(HCC) is the fourth most common cancer type worldwide, with a poor prognosis and high mortality rate. The aim of the present study was to investigate the mechanisms underlying HCC progression to potentially benefit the development of effective therapies for advanced HCC. The present study reported a novel mechanism that promotes the HCC malignant phenotype, in which the inhibitor of differentiation 1(ID1) activates the aurora kinase A(AURKA)/Myc signaling pathway. Specifically, a high expression of ID1 promoted a highly malignant phenotype of HCC cells that exhibit enhanced metastatic ability and drug resistance. However, the effects of ID1 were markedly reversed by the AURKA inhibitor VX689 and the Myc inhibitor 10058‑F4. Further studies demonstrated that ID1 competitively binds with anaphase‑promoting complex/cyclosome Cdh1(APC/CCdh1), which is responsible for ubiquitination‑mediated AURKA protein degradation, resulting in upregulation of AURKA. Increased AURKA expression subsequently enhanced Myc expression at both transcriptional and post‑transcriptional level, leading to amplification of the Myc oncogenic signaling pathway. This novel ID1/AURKA/Myc axis could be a promising therapeutic target for the development of effective therapeutic strategies for advanced HCC.
Highlights
Hepatocellular carcinoma (HCC) was the sixth most commonly diagnosed cancer and the third leading cause of cancer‐associated mortality worldwide in 2018, with a 5‐year relative survival rate of
Patients with HCC exhibit an overexpression of inhibitor of differentiation 1 (ID1), which is associated with poor prognosis
Survival analysis using the Guichard_Liver dataset revealed that a high expression of ID1 gene was significantly associated with a poor recurrence‐free survival rate [hazard ratio (HR), 1.865; P
Summary
Hepatocellular carcinoma (HCC) was the sixth most commonly diagnosed cancer and the third leading cause of cancer‐associated mortality worldwide in 2018, with a 5‐year relative survival rate of
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