Objective:

23:T4f3, Objective:

The aim of this study was to evaluate whether ubiquitin-specific peptidase 26 (USP26) gene variations were associated with nonobstructive azoospermia (NOA).

Methods:

Seven hundred and seventy-six patients diagnosed with NOA and 709 proven fertile men were included in this study. Genetic variations of infertility-related genes, including USP26, were identified by selected exonic sequencing. The effects of USP26 mutations on androgen receptor (AR) binding, ubiquitination, and transcriptional activity were detected by immunoprecipitation and luciferase assay in Hela and TM4 cells.

Results:

Six novel missense mutations and 1 novel synonymous mutation of USP26 unique to the patients with NOA were identified. Of these missense mutations, USP26 R344W remarkably reduced the binding affinity and deubiquitinating activity of USP26 to AR, thus eliminated the inhibitory effect of USP26 on transcriptional activity of AR in Hela and TM4 cells.

Conclusion:

A novel USP26 variant p.R344W is associated with NOA probably through affecting AR function.

24:T449,

Gastric cancer is one of the leading causes of cancer mortality worldwide, but the underlying molecular mechanisms by which gastric cancer progresses are not fully understood. While deubiquitinases have emerged as promising therapeutic targets in various cancers, a suitable target deubiquitinase for the treatment of gastric cancer has not yet been identified. Using bioinformatics analyses, we identified that upregulation of ubiquitin-specific peptidase 26 (USP26) was associated with poor patient survival in patients with gastric cancer; moreover, depletion of endogenous USP26 with short hairpin RNAs significantly suppressed the aerobic glycolysis and proliferation in tumor cells. In mechanism, USP26 was revealed to interact with and stabilize c-Myc, which is a key driver of tumor metabolism and carcinogenesis, via suppressing its polyubiquitination and degradation. In summary, these findings suggest that USP26 plays a novel oncogenic role of USP26 by forming a USP26–c-Myc regulatory axis, and that targeting USP26 may be a potential therapeutic strategy for gastric cancer.

Search results

A Novel Missense Mutation in USP26 Gene Is Associated With Nonobstructive Azoospermia

USP26 Promotes Cell Proliferation of Gastric Cancer by Stabilizing c-Myc