RFX1: a promising therapeutic arsenal against cancer

Abstract

Regulatory factor X1 (RFX1) is an evolutionary conserved transcriptional factor that influences a wide range of cellular processes such as cell cycle, cell proliferation, differentiation, and apoptosis, by regulating a number of target genes that are involved in such processes. On a closer look, these target genes also play a key role in tumorigenesis and associated events. Such observations paved the way for further studies evaluating the role of RFX1 in cancer. These studies were indispensable due to the failure of conventional chemotherapeutic drugs to target key cellular hallmarks such as cancer stemness, cellular plasticity, enhanced drug efflux, de-regulated DNA repair machinery, and altered pathways evading apoptosis. In this review, we compile significant evidence for the tumor-suppressive activities of RFX1 while also analyzing its oncogenic potential in some cancers. RFX1 induction decreased cellular proliferation, modulated the immune system, induced apoptosis, reduced chemoresistance, and sensitized cancer stem cells for chemotherapy. Thus, our review discusses the pleiotropic function of RFX1 in multitudinous gene regulations, decisive protein–protein interactions, and also its role in regulating key cell signaling events in cancer. Elucidation of these regulatory mechanisms can be further utilized for RFX1 targeted therapy.

Hypoxia-induced exosomes facilitate lung pre-metastatic niche formation in hepatocellular carcinoma through the miR-4508-RFX1-IL17A-p38 MAPK-NF-κB pathway

“…Notably, this represented the major function of RFX1. Previous studies have described both the tumor-suppressive and oncogenic roles of RFX1, which involve the regulation of proliferation, the immune system, stemness, and chemoresistance 27 , 28 . To confirm that RFX1 is a binding target of miR-4508, a dual-luciferase assay was performed.…”

“…Although RFX1 knockdown activated p38 MAPK and NF-κB signaling in fibroblasts, the links between RFX1 and p38 MAPK/NF-κB have not previously been established. RFX1 not only targets oncogenes (such as c-MYC ) but also downregulates some inflammation-related genes with pro-tumor activities (such as TGF-β2 , IL17A , and TLR4 ) 27 . Numerous studies have indicated that IL17A promotes the release of inflammatory factors and contributes to the development of pulmonary fibrosis 59 , 60 .…”

PRDM6 promotes medulloblastoma by repressing chromatin accessibility and altering gene expression

“…The binding of RFX and SOX family was most strongly impaired by PRDM6 expression in NES cells (Figure 4B). Notably, RFX transcription factors, including RFX1 16 , have been implicated in tumor suppression 17 , suggesting that reduced binding of these transcription factors in the presence of PRDM6 may have oncogenic potential in NES cells. Moreover, the binding of other transcription factors with roles in genome organization, development, and cell fate was affected ( Table S3 ).…”

“…Our footprinting analysis shows significantly altered binding of transcription factors to open chromatin regions in PRDM6 NES cells. These include RFX1, a transcriptional repressor of tumor suppressors, and several other RFX transcription factors 16 . Notably, multiple RFX1 target genes, including the oncogene FGF1 , COL1A1 , and COL1A2 , are upregulated in PRDM6 NES cells.…”

Clinical Significance of Apurinic/Apyrimidinic Endodeoxyribonuclease 1 and MicroRNA Axis in Hepatocellular Carcinoma

“…Nevertheless, miR-3180-3p was reported to downregulate regulatory factor X1 (also referred to as RFX1 ), 49 which has both anticancer and cancer-promoting activities. 50 Indeed, it can regulate the expression of several proto-oncogenes as well as tumor suppressors, depending on tumor type and on spatial and temporal expression. 50 Thus, the interpretation of our results still needs more evidence about the role of this miRNA in cancer.…”