Meta-analysis of gene expression alterations and clinical significance of the HECT domain-containing ubiquitin ligase HUWE1 in cancer

摘要

E3 ubiquitin-protein ligase (HUWE1) has previously been identified as a HECT domain-containing ubiquitin ligase (E3) that is involved in several signaling pathways, transcriptional regulation, neural differentiation, DNA damage responses and apoptosis. However, the function of HUWE1 in the various types of cancer remains unclear. A previous study indicated that HUWE1 exhibited different roles depending on the cancer type due to the ubiquitination of various substrates. The objective of the present study was to determine whether HUWE1 can be employed as a prognostic indicator in human cancer. The expression of HUWE1 was examined using the Oncomine database, and gene alterations during carcinogenesis, copy number alterations and mutations of HUWE1 were then analyzed using cBioPortal, which is the International Cancer Genome Consortium and the Tumorscape database. Furthermore, the association between HUWE1 expression and patient survival was evaluated using Kaplan-Meier plotter and the PrognoScan databases. In addition, the present study attempted to establish the functional association between HUWE1 expression and cancer phenotypes, and the results revealed that HUWE1 may serve as a diagnostic marker or therapeutic target for certain types of cancer. HUWE1 may serve an oncogenic role in breast, brain and prostate cancer, while it may serve an anti-oncogenic role in colorectal cancer and certain lung cancers. The function of HUWE1 and its mechanisms require more in-depth and extensive investigation in future studies.