Ubiquitination-related Gene UBTD1 Mediates Poor Prognosis of Colorectal Cancer and Affects Colorectal Cancer Cell Proliferation and Ferroptosis.

Abstract

Background: Colorectal cancer (CRC) is the third most common cancer worldwide, and its occurrence and progression are often regulated by genetic and hereditary factors. Ubiquitination and the associated ubiquitin-binding enzymes and ligases regulate the tumor microenvironment and antitumor immunity to mediate tumor pathogenesis and progression. In this study, we examined the molecular characteristics and immunomodulatory effects of ubiquitination-associated genes that mediate CRC prognosis.

Methods: The ubiquitination-related gene ubiquitin domain-containing protein 1 (UBTD1) was identified using bioinformatics and single-cell analyses. Subsequently, the ability of UBTD1 to predict CRC prognosis and immune checkpoint correlation was analyzed, the potential drug telatinib targeting UBTD1 was explored, and the correlation between UBTD1 and ferroptosis was analyzed. The role of UBTD1 in CRC and ferroptosis was verified using immunohistochemistry, gene knockout, western blot, cell cloning, and immunofluorescence.

Results: UBTD1 was identified as a significant prognostic and predictive gene for CRC and was involved in regulating immune checkpoint levels and immune cell function of CRC patients with CRC. High UBTD1 expression was found to enhance the presence of immune checkpoints that induce immune escape and inhibit ferroptosis onset. Telatinib may be a potential therapeutic drug targeting UBTD1.

Conclusion: Our study demonstrated that UBTD1 is a prognostic marker for CRC in the regulation of ubiquitination and the tumor immune microenvironment and may serve as a modulator of ferroptosis.