Ptrh1-KO Mouse

Ptrh1, or peptidyl-tRNA hydrolase 1 homolog, is an RNA binding protein (RBP) [1]. It is involved in the ribosome-associated quality control (RQC) pathway, where it can cleave non-ubiquitinated NC-tRNA in non-ubiquitinated 60S ribosome-nascent chain complexes (60S RNCs) and 80S RNCs formed on non-stop mRNAs, suggesting a pathway for the release of non-ubiquitinated nascent chains (NCs) [2].

In pancreatic cancer, high glucose downregulates Ptrh1 through RAS signaling following EGFR stimulation. This downregulation enhances the stability of the PD-L1 mRNA, leading to increased PD-L1 expression. Overexpression of Ptrh1 in pancreatic cells suppresses PD-L1 expression and improves the proportion and cytotoxic function of CD8+ T cells in the pancreatic tumor microenvironment (TME) of diabetic mice, indicating its importance in anti-tumor immunity in the pancreatic TME [1].

In colorectal cancer, Ptrh1 is one of the eight prognosis-related RBPs identified. It was selected, along with three other RBPs, to construct a prognostic risk score model that accurately predicted the prognosis of CRC patients [3]. In another study, Ptrh1 was included in a five-gene prognostic signature for CRC, suggesting its role in the pathogenesis and prognosis of CRC [4].

In conclusion, Ptrh1 is a significant RBP involved in the RQC pathway and has implications in multiple disease conditions. Studies, especially those using mouse models in pancreatic and colorectal cancer, have revealed its crucial role in tumor-related immune regulation and prognosis, providing insights into potential therapeutic strategies for these diseases.