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Published on: September 1, 2019
Pan-cancer investigation of RFX family and associated genes identifies RFX8 as a therapeutic target in leukemia
Zelong Cui1, Yue Fu1,2, Minran Zhou1
1Department of Hematology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
Background:
Several transcription factors and co-factors are encoded by the RFX (Regulatory Factor X) family (RFX1-8) and associated genes (RFXAP and RFXANK). Increasing evidence suggests that the RFX family and associated genes are involved in the development and progression of cancer. However, no prior research has focused on a multi-omic analysis of these genes to evaluate their role in tumor progression.
Methods:
Using combined TCGA and GTEx pan-cancer data, we investigated the expression patterns and survival profiles of these ten genes. We then focused on RFX8 to analyze its clinicopathological and therapeutic features. Finally, we conducted experimental validation of RFX8 function in acute myeloid leukemia (AML).
Results:
RFX5 and RFXANK showed higher expression levels, while RFX6 showed lower expression levels in most types of cancer, with RFX8 being the most upregulated in LAML. RFX2 and RFXAP demonstrated prognostic significance in eight types of cancer, and RFX8 showed significance in six types of cancer. The expression of these ten genes exhibited specific characteristics in immune subtypes, tumor microenvironment, and stemness. The expression of RFX8 was correlated with various tumor stages, microsatellite instability (MSI), tumor mutation burden (TMB), immune cell infiltration, and immune-checkpoint expression. Additionally, RFX8 was found to regulate tumorigenesis and sensitivity to chelerythrine in AML.
Conclusions:
Our work delineated the landscape of the RFX family and associated genes in the pan-cancer context and the specific role of RFX8 in AML. These findings might offer cues for further investigations of these genes in cancer biology.
Insights
The RFX gene family plays a role in cancer progression. RFX8 is notably upregulated in acute myeloid leukemia (AML) and influences tumorigenesis and treatment response.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The RFX (Regulatory Factor X) gene family, including RFX1-8, RFXAP, and RFXANK, encodes transcription factors and co-factors.
- Emerging evidence links RFX family genes to cancer development and progression.
- A comprehensive multi-omic analysis of these genes in cancer has been lacking.
Purpose of the Study:
- To conduct a pan-cancer analysis of RFX family and associated genes' expression and prognostic value.
- To investigate the clinicopathological and therapeutic relevance of RFX8.
- To experimentally validate RFX8's function in acute myeloid leukemia (AML).
Main Methods:
- Utilized combined TCGA and GTEx pan-cancer datasets for expression and survival analysis.
- Focused on RFX8 for detailed clinicopathological and therapeutic feature analysis.
- Performed experimental validation of RFX8 in AML models.
Main Results:
- RFX5 and RFXANK were upregulated, while RFX6 was downregulated across many cancers; RFX8 showed highest upregulation in LAML.
- RFX2, RFXAP, and RFX8 demonstrated significant prognostic value in multiple cancer types.
- RFX8 expression correlated with tumor stage, MSI, TMB, immune infiltration, and immune-checkpoint expression.
- RFX8 was experimentally shown to regulate tumorigenesis and chelerythrine sensitivity in AML.
Conclusions:
- This study provides a comprehensive landscape of the RFX gene family in pan-cancer analysis.
- RFX8 plays a specific and significant role in AML progression and therapeutic response.
- Findings offer potential targets for future cancer research and therapeutic strategies.
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