Downregulation of ZNF280A inhibits proliferation and tumorigenicity of colorectal cancer cells by promoting the ubiquitination and degradation of RPS14

Colorectal cancer (CRC), one of the cancers with highest mortality, involves complicated molecular mechanisms leading to the onset of malignant phenotypes. ZNF280A, a member of the zinc-finger protein family, was shown to be a promotor of oncogenesis in CRC in this study. ZNF280A was remarkably upregulated in CRC tissues, which was meaningfully associated with tumor progression and poor prognosis in patients with CRC. Loss-of-function studies revealed that ZNF280A knockdown inhibited the development and progression of CRC as evident by the inhibition of cell proliferation, colony formation, cell apoptosis, cell cycle distribution, and cell migration in vitro and the repressed tumorigenesis of CRC cells in vivo. Next, we showed that RPS14 was the downstream target of ZNF280A and ZNF280A knockdown promoted the ubiquitination as well as degradation of RPS14 in CRC. Additionally, we demonstrated that RPS14 regulated the development of CRC via PI3K-Akt signaling pathway. Taken together, our findings provide a novel clear insight into ZNF280A/RPS14/PI3K-Akt axis in CRC for the first time, offering a potential target for early detection, diagnosis and treatment of CRC in future clinical applications.

Automated summary

This study reveals that ZNF280A overexpression is associated with tumor progression and poor prognosis in colorectal cancer (CRC), and its knockdown inhibits the development and progression of CRC. Furthermore, ZNF280A regulates CRC through the downstream target RPS14 and the PI3K-Akt signaling pathway.