Dkc1-flox Mouse

Dkc1, also known as dyskerin pseudouridine synthase 1, is associated with the formation of certain small RNAs and telomerase activity [5]. Mutations in DKC1 can lead to dyskeratosis congenita, a rare hereditary disease [3]. In normal biological processes, it may be involved in pathways related to cell proliferation, ribosome biogenesis, and telomere maintenance.

DKC1 has been found to play a significant role in multiple cancers. In colorectal cancer, DKC1 promotes cell proliferation by binding to and stabilizing the mRNA of several ribosomal proteins, and its knockdown attenuates cell growth. Dual inhibition of DKC1 and MEK1/2 synergistically restrains colorectal cancer cell growth [1].

In pancreatic ductal adenocarcinoma, SENP3 interacts with DKC1 and catalyzes its deSUMOylation, causing DKC1 instability and impairing cell migration. Overexpression of DKC1 abates the anti-metastasis effect of SENP3 [2].

In lung adenocarcinoma, DKC1 is overexpressed, and its knockdown induces G1 phase arrest, inhibits cell proliferation, and leads to telomere-related senescence and apoptosis [4].

In glioma, DKC1 expression is increased, and its knockdown inhibits cell growth, migration, and invasion [5].

In gastric cancer, DKC1 aggravates cell migration and invasion through up-regulating the expression of TNFAIP6 [6].

In neuroblastoma, DKC1 is highly expressed, and its knockout decreases cell activity, proliferation, invasion, and migration while increasing apoptosis [7]. A meta-analysis also shows that high DKC1 expression is predictive of worse prognosis and poorer clinicopathological parameters in malignancies [8].

In conclusion, Dkc1 is crucial for normal cellular functions, especially those related to ribosome production and telomerase complex function. Its dysregulation significantly impacts the development and progression of various cancers, such as colorectal, pancreatic, lung, glioma, gastric, and neuroblastoma cancers. The findings from loss-of-function experiments in these contexts have enhanced our understanding of Dkc1's role in disease, suggesting it could be a potential therapeutic target.