The discovery of novel and critical genes implicated in malignant development is a topic of high interest in cancer research. Intriguingly, a group of genes named "double-agent" genes were reported to have both oncogenic and tumor-suppressive functions. To date, less than 100 "double-agent" genes have been documented. Fubp1 is a master transcriptional regulator of a subset of genes by interacting with a far upstream element (FUSE). Mounting evidence has collectively demonstrated both the oncogenic and tumor suppressive roles of Fubp1 and the debate regarding its roles in tumorigenesis has been around for several years. Therefore, the detailed molecular mechanisms of Fubp1 need to be determined in each context. In the present study, we showed that the Fubp1 protein level was enriched in the S phase and we identified that Fubp1 deficiency altered cell cycle progression, especially in the S phase, by downregulating the mRNA expression levels of Ccna genes encoding cyclin A. Although this Fubp1-cyclin A axis appears to exist in several types of tumors, Fubp1 showed heterogeneous expression patterns among various cancer tissues, suggesting it exhibits multiple and complicated functions in cancer development. In addition, we showed that Fubp1 deficiency confers survival advantages to cells against metabolic stress and anti-cancer drugs, suggesting that Fubp1 may play both positive and negative roles in malignant development.
Keywords: Fubp1; cell cycle; cell death; cyclin A; double-agent; lung cancer.