Wdr43-flox Mouse

Wdr43, also known as Utp5 in yeast, is an essential ribogenesis factor. It functions as a chromatin-associated RNA-binding protein (RBP) and release factor, modulating polymerase (Pol) II activity for pluripotency regulation. Wdr43 binds to promoter-associated noncoding/nascent RNAs, occupies gene promoters and enhancers, and interacts with the Pol II machinery [2]. It is also involved in ribosome biogenesis, which is crucial for normal development and cell function [3,5].

In colorectal cancer, Wdr43 knockdown significantly inhibits cell growth by arresting the cell cycle and enhancing the effect of oxaliplatin chemotherapy both in vitro and in vivo. Mechanistically, c-MYC promotes Wdr43 transcription upon oxaliplatin stimulation, and Wdr43 enhances p53 ubiquitination by MDM2, reducing p53 protein stability and promoting cancer cell proliferation and chemoresistance [1].

In non-small cell lung cancer, knocking down Wdr43 expression significantly impairs cell migration, proliferation, and causes cell-cycle arrest in the G1 phase [4].

In colorectal cancer, Wdr43 knockdown increases apoptosis, inhibits cell proliferation, migration, and invasion in vitro and reduces tumorigenesis in animal models, and its effect can be partially reversed by overexpressing vimentin [6].

In conclusion, Wdr43 plays a significant role in ribosome biogenesis and pluripotency regulation. In disease conditions, especially in cancers like colorectal and non-small cell lung cancer, Wdr43 promotes tumor progression. The study of Wdr43 through loss-of-function experiments in cell lines and animal models has provided valuable insights into its role in cancer development, suggesting it could be a potential therapeutic target.