Multiple Functions of Fubp1 in Cell Cycle Progression and Cell Survival

Abstract

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.

FUBP1 promotes the proliferation of lung squamous carcinoma cells and regulates tumor immunity through PD-L1

“…For example, FUBP1 is involved in cell survival and cell cycle progression. 7 RARS-MAD1L1 fusion gene might serve as an attractive target for therapeutic intervention for nasopharyngeal carcinoma (NPC) through the FUBP1-c-Myc axis. 8 FUBP1 serves as a cancer operator and widespread regulator of tumor suppressor, and FUBP1 participates in regulating mechanistically N6-methyladenosine (m6A) RNA methylation.…”

Pan-Cancer Transcriptome and Immune Infiltration Analyses Reveal the Oncogenic Role of Far Upstream Element-Binding Protein 1 (FUBP1)

“…FUBP1 has been reported to be a DNA- and RNA-binding protein involved in the processes of transcription, translation, and alternative splicing ( Debaize et al, 2018 ; Debaize and Troadec, 2019 ; Elman et al, 2019 ; Kang et al, 2020 ). The phylogenetic tree analysis conducted in our study demonstrated the highly conserved nature of this protein across different species, suggesting the shared expression of FUBP1 among common ancestors of humans and animals and indicating that there may be a similar mechanism in various physiological and pathological processes.…”

A pleiotropic variant in DNAJB4 is associated with multiple myeloma risk

“…FUBP1 encodes a multifunctional DNA and RNA‐binding protein involved in cell cycle regulation and self‐renewal of hematopoietic stem cells (HSCs) 47 . FUBP1 acts both as oncogene and as tumor suppressor, and its activity is tissue‐dependent 48 . In various tumor types FUBP1 promotes the overexpression of the MYC oncogene, 48 whereas FUBP1 silencing does not influence the expression of MYC in normal fibroblasts, prostate and bladder cancer cells 48 .…”

“…FUBP1 acts both as oncogene and as tumor suppressor, and its activity is tissue‐dependent 48 . In various tumor types FUBP1 promotes the overexpression of the MYC oncogene, 48 whereas FUBP1 silencing does not influence the expression of MYC in normal fibroblasts, prostate and bladder cancer cells 48 . Moreover, FUBP1 is involved in the upregulation and downregulation of the cell cycle inhibitor p21 49,50 .…”

“… 48 In various tumor types FUBP1 promotes the overexpression of the MYC oncogene, 48 whereas FUBP1 silencing does not influence the expression of MYC in normal fibroblasts, prostate and bladder cancer cells. 48 Moreover, FUBP1 is involved in the upregulation and downregulation of the cell cycle inhibitor p21 . 49 , 50 The pleiotropic role of rs34517439 could be explained by its involvement in the altered expression of FUBP1 in different tumors, that determines their development, by interacting with specific factors in each tissue.…”