RFX1: a promising therapeutic arsenal against cancer
Joby Issac1, Pooja S Raveendran1, Ani V Das2
1Cancer Research Program, Rajiv Gandhi Centre for Biotechnology, Thycaud.P.O, Thiruvananthapuram, 695014, Kerala, India.
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.
Insights
Regulatory Factor X1 (RFX1) shows tumor-suppressive roles in cancer by inhibiting proliferation and enhancing chemotherapy sensitivity. However, RFX1 also exhibits oncogenic potential in certain cancers, highlighting its complex role.
Area of Science:
- Molecular Biology
- Cancer Research
- Genetics
Background:
- Regulatory Factor X1 (RFX1) is a conserved transcription factor regulating cell cycle, proliferation, differentiation, and apoptosis.
- RFX1 target genes are implicated in tumorigenesis, necessitating investigation into its role in cancer.
- Conventional chemotherapy often fails against cancer hallmarks like stemness and drug resistance.
Purpose of the Study:
- To review the dual role of RFX1 as both a tumor suppressor and an oncogene in various cancers.
- To analyze RFX1's impact on cellular processes critical to cancer progression and treatment resistance.
- To explore RFX1's potential for targeted cancer therapy.
Main Methods:
- Literature review compiling evidence on RFX1's function in cancer.
- Analysis of RFX1's effects on cell proliferation, immune modulation, apoptosis, and chemoresistance.
- Examination of RFX1's role in regulating gene expression, protein interactions, and cell signaling pathways.
Main Results:
- RFX1 demonstrates tumor-suppressive activities, decreasing proliferation and inducing apoptosis.
- RFX1 induction enhances chemoresistance and sensitizes cancer stem cells to chemotherapy.
- RFX1 exhibits oncogenic potential in specific cancer types, indicating context-dependent functions.
Conclusions:
- RFX1 possesses pleiotropic functions in cancer, acting as both a tumor suppressor and an oncogene.
- Understanding RFX1's regulatory mechanisms is crucial for developing targeted therapeutic strategies.
- RFX1-targeted therapy holds promise for overcoming treatment resistance and improving cancer outcomes.
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