Ubiquitin-specific peptidase 28 mRNA (USP28 mRNA)

Ubiquitin-specific peptidase 28 (USP28) mRNA is the messenger RNA transcript that encodes the USP28 protein, a member of the ubiquitin-specific protease family of deubiquitinating enzymes. The USP28 protein plays a critical role in maintaining the stability of essential oncogenic transcription factors and cell cycle regulators, such as c-Myc, FBW7, and cyclin E, by removing their polyubiquitin chains and preventing proteasomal degradation (Popov et al., 2007, Nature). In many human cancers, including colorectal, lung, and breast cancer, USP28 is frequently overexpressed, leading to the pathological stabilization of these oncogenes and promoting tumor growth, metastasis, and resistance to apoptosis (Prieto et al., 2021, Frontiers in Cell and Developmental Biology). Targeting USP28 at the mRNA level using RNA interference (RNAi) or antisense oligonucleotides (ASOs) provides a strategy to reduce the overall protein expression, thereby indirectly promoting the degradation of its oncogenic substrates (Zhang et al., 2018, Oncology Reports). This therapeutic approach is currently being explored in preclinical models to overcome the challenges associated with developing highly selective small-molecule inhibitors for the USP28 catalytic site. By depleting the mRNA pool, researchers aim to disrupt the USP28-c-Myc axis, which is a major driver of proliferation in various malignancies (Diefenbacher et al., 2014, Journal of Clinical Investigation).

Other names

Ubiquitin carboxyl-terminal hydrolase 28 mRNAUSP28 transcriptUSP28 messenger RNA

RNA interference or antisense-mediated degradation of mRNA to prevent translation of the USP28 protein