Oncogenic Potential of Replication Factor C Subunit 4: Correlations with Tumor Progression and Assessment of Potential Inhibitors

Author:

Alaa Eldeen Muhammad1ORCID,Mamdouh Farag2ORCID,Abdulsahib Waleed K.3ORCID,Eid Refaat A.4ORCID,Alhanshani Ahmad A.5,Shati Ayed A.5ORCID,Alqahtani Youssef A.5,Alshehri Mohammed A.5ORCID,Samir A. Zaki Mohamed6ORCID,Soltan Mohamed A.7ORCID,Noreldin Ahmed E.8ORCID

Affiliation:

1. Cell Biology, Histology & Genetics Division, Zoology Department, Faculty of Science, Zagazig University, Zagazig 44519, Egypt

2. Biotechnology Division, Zoology Department, Faculty of Science, Benha University, Al Qalyubia Governorate, Banha 13511, Egypt

3. Pharmacology and Toxicology Department, College of Pharmacy, Al Farahidi University, Baghdad 00965, Iraq

4. Pathology Department, College of Medicine, King Khalid University, Abha P.O. Box 62529, Saudi Arabia

5. Department of Child Health, College of Medicine, King Khalid University, Abha P.O. Box 62529, Saudi Arabia

6. Anatomy Department, College of Medicine, King Khalid University, Abha P.O. Box 62529, Saudi Arabia

7. Department of Microbiology and Immunology, Faculty of Pharmacy, Sinai University, Ismailia 41611, Egypt

8. Department of Histology and Cytology, Faculty of Veterinary Medicine, Damanhour University, Damanhour 22511, Egypt

Abstract

Replication Factor C Subunit 4 (RFC4), an oncogene implicated in many human cancers, has yet to be extensively studied in many cancer types to determine its expression patterns and tumor tissue function. Various bioinformatics tools were used to analyze RFC4 as a potential oncogene and therapeutic target across many cancers. We first examined RFC4 expression levels in several human tumor types to determine relationships with tumor grade, stage, metastasis, and patient survival. We also examined RFC4’s genetic changes, epigenetic methylation, and effect on tumor microenvironment (TME) immune cell infiltration. We also analyzed RFC4’s connections with immunological checkpoints to identify potential molecular pathways involved in carcinogenesis. Our findings show that RFC4 is upregulated in several tumor types and associated with poor prognoses in many human cancers. This study shows that RFC4 significantly affects the tumor immunological microenvironment, specifically immune cell populations. Finally, we screened for RFC4-inhibiting pharmacological compounds with anti-cancer potential. This study fully elucidates RFC4’s carcinogenic activities, emphasizing its potential as a prognostic biomarker and a target for anti-cancer therapy.

Funder

Deanship of Scientific Research at King Khalid University

Publisher

MDPI AG

Subject

Drug Discovery,Pharmaceutical Science,Molecular Medicine

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