RFX1: a promising therapeutic arsenal against cancer

Joby Issac,Ani V Das,Pooja S Raveendran

doi:10.1186/s12935-021-01952-6

Joby Issac, Ani V Das + Show 1 more

Open Access

https://doi.org/10.1186/s12935-021-01952-6

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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.

Highlights

Regulatory factor X1 (RFX1) is a context-dependent transcription factor that can regulate gene expression differently based on the target gene but independent of cellular habitat [1]
Cancer cells are difficult to target as they exploit key processes like cell proliferation, differentiation, and apoptosis by modulating the expression of key molecules involved in the regulation of such activities [5]
A similar study using glioblastoma cell lines proved that RFX1 overexpression led to decreased cell invasion, migration, and proliferation mediated by direct targeting of CD44 [2]

Summary

Introduction

Regulatory factor X1 (RFX1) is a context-dependent transcription factor that can regulate gene expression differently based on the target gene but independent of cellular habitat [1]. RFX1 promotes differentiation of CSCs by directly and indirectly targeting major stemness regulators like c-Myc, FGF1, and CD44. It is clear that the altered expression and cancer types are crucial in interpreting RFX1 mediated gene regulation.

Results

Conclusion