Abstract
Liver cancer is one of the most lethal human malignancies in the world. Although great efforts have been made to develop novel therapeutic targets, effective drug targeting remains limited. C20orf27, located on human chromosome 20, is a gene whose function has not been fully elucidated. In this study, we identified C20orf27 as a critical gene that facilitates liver cancer progression. We detected that C20orf27 was upregulated in liver cancer samples. Gain- and loss-of-function experiments demonstrated that C20orf27 enhanced liver cancer cell proliferation and migration by regulating cyclin-related proteins, including MDM2, PCNA, Cyclin E1, CDK2, and p-Rb. RNA sequencing and bioinformatics analyses revealed that NT5E, ACE, and TTR were potential downstream targets of C20orf27. Immunohistochemistry analysis of tissue microarrays suggested that NT5E expression was significantly associated with C20orf27 levels. Moreover, the combination of C20orf27 and NT5E predicted the prognosis of liver cancer patients, as higher levels of both were associated with poorer overall survival and disease-free survival after surgery. Our findings are the first to report the functional role of the C20orf27/NT5E axis in promoting hepatocellular carcinoma progression, highlighting its potential as a novel therapeutic target and biomarker for HCC.