tRNA queuosine modification enzyme modulates the growth and microbiome recruitment to breast tumors
Abstract Background: Transfer RNA (tRNA) queuosine (Q)-modifications occur specifically in 4 cellular tRNAs at the wobble anticodon position. tRNA Q-modification in human cells depends on the gut microbiome because the microbiome product queuine is required for its installation by the enzyme queuine tRNA ribosyltransferase catalytic subunit 1 (QTRT1) encoded in the human genome. Although tRNA Q-modification has been studied a long time regarding its properties in decoding and tRNA fragment generation, how QTRT1 affects tumorigenesis is still poorly understood. Results: We generated single clones of QTRT1-knockout breast cancer MCF7 cells using Double Nickase Plasmid. The impacts of QTRT1-delection on cell proliferation and migration in vitro were evaluated using cell culture, while the regulations on tumor growth in vivo were evaluated using xenograft BALB/c nude mouse model. We found that QTRT1 completely deleted from human breast cancer MCF7 cells could change the functions of regulation genes which are critical in cell proliferation, tight junction formation, and migration in human breast cancer cells in vitro and a breast tumor mouse model in vivo . We also found that microbiome maybe involved in the breast cancer development in vivo. Conclusions: Our results demonstrate that the QTRT1 gene and microbiome play a critical role in breast cancer development.