Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Oncology Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1021-335X Online ISSN: 1791-2431
Journal Cover
December-2025 Volume 54 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
December-2025 Volume 54 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Review Open Access

Multiple roles of replication factor C family in pan‑cancer (Review)

  • Authors:
    • Dan Luo
    • Bo Li
    • Xueping Jiang
  • View Affiliations / Copyright

    Affiliations: The Minda Hospital, Hubei Minzu University, Enshi, Hubei 445000, P.R. China, Hubei Selenium and Human Health Institute, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, Hubei 445000, P.R. China
    Copyright: © Luo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 165
    |
    Published online on: September 25, 2025
       https://doi.org/10.3892/or.2025.8998
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Due to the persistently high global incidence and mortality rates of cancer, developing novel therapeutic strategies is imperative. The replication factor C (RFC) family, a critical subset of DNA replication and repair, serves multifaceted roles in tumor progression. Despite its widely recognized importance, the pleiotropic mechanisms of the RFC family lack systematic illustration, particularly regarding each member specific contributions to cancer hallmarks. In the present review, mRNA expression of each RFC family member in pan‑cancer was profiled and the associations between their expression levels and tumor types evaluated. In addition, the effect of RFC expression on patients' survival across malignancies is assessed. Furthermore, the present review summarized current research on RFC family members in various malignancies with particular emphasis on the RFC‑like complexes, highlighting key findings and advancements in understanding their role in tumor biology. The signaling pathways associated with RFC family members are discussed and the molecular mechanisms elucidated. Finally, the clinical importance of RFC family members including prognosis, potential inhibitors and combination treatments are also discussed. The present review aimed to provide innovative perspectives for developing combinatorial molecular targeted therapies in the future.
View Figures

Figure 1

RFC boxes in each family member. RFC,
replication factor C.

Figure 2

Differential expression of RFC
subunits in various tumors. The dot plot represents the gene
expression profiles of all tumor samples and paired normal tissues.
The expression levels of (A) RFC1, (B) RFC2, (C) RFC3, (D) RFC4 and
(E) RFC5 in pan-cancer from The Cancer Genome Atlas database were
analyzed using Tumor IMmune Estimation Resource 2.0. RFC,
replication factor C. *P<0.05, **P<0.01 and
***P<0.001.

Figure 3

Clinical relevance of RFC family in
pan-cancer. (A) The functional heatmap shows the clinical relevance
of gene expression across various cancer types. Based on the (B)
highest and (C) lowest Z scores for each cancer type, the
association between each RFC subunits mRNA expression and OS in
patients with various cancers was analyzed. RFC, replication factor
C; OS, overall survival.

Figure 4

Roles of RFC subunits in different
signaling pathways. RFC2 participates in the FOXO1 and PI3K/AKT
signal pathways. RFC3 participates in the YAP1/TEAD1 and
Wnt/β-catenin signal pathways. RFC4 participates in Notch1
signaling pathway. ↑, increase; ↓, decrease; RFC, replication
factor C; FOXO1, Forkhead box protein O1; YAP1, yes-associated
protein 1; TEAD, TEA domain family member 1; p-, phosphorylated;
PARP, poly(ADP-ribose) polymerase; EMT, epithelial-mesenchymal
transition GSK3β, glycogen synthase kinase-3 β; GPX4, glutathione
peroxidase 4.

Figure 5

Protein-protein interaction network
of RFC family members relevant genes. RFC, replication factor
C.

Figure 6

Enrichment analysis based on (A) GO
and (B) KEGG pathway analysis. GO, gene ontology; KEGG, Kyoto
Encyclopedia of Genes and Genomes.

Figure 7

Map of RFC subunits and multiple
tumors. RFC, replication factor C.
View References

1 

Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I and Jemal A: Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 74:229–263. 2024.

2 

Uhlmann F, Gibbs E, Cai J, O'Donnell M and Hurwitz J: Identification of regions within the four small subunits of human replication factor C required for complex formation and DNA replication. J Biol Chem. 272:10065–10071. 1997. View Article : Google Scholar

3 

Zhao X, Wang Y, Li J, Qu F, Fu X, Liu S, Wang X, Xie Y and Zhang X: RFC2: A prognosis biomarker correlated with the immune signature in diffuse lower-grade gliomas. Sci Rep. 12:31222022. View Article : Google Scholar

4 

Yao Z, Hu K, Huang HE, Xu S, Wang Q, Zhang P, Yang P and Liu B: shRNA-mediated silencing of the RFC3 gene suppresses hepatocellular carcinoma cell proliferation. Int J Mol Med. 36:1393–1399. 2015. View Article : Google Scholar

5 

Guo Z and Guo L: Abnormal activation of RFC3, A YAP1/TEAD downstream target, promotes gastric cancer progression. Int J Clin Oncol. 29:442–455. 2024. View Article : Google Scholar

6 

Misbah M, Kumar M, Najmi AK and Akhtar M: Identification of expression profiles and prognostic value of RFCs in colorectal cancer. Sci Rep. 14:66072024. View Article : Google Scholar

7 

Lou F and Zhang M: RFC2 promotes aerobic glycolysis and progression of colorectal cancer. BMC Gastroenterol. 23:3532023. View Article : Google Scholar

8 

Li H, Chai L, Ding Z and He H: CircCOL1A2 sponges MiR-1286 to promote cell invasion and migration of gastric cancer by elevating expression of USP10 to downregulate RFC2 ubiquitination level. J Microbiol Biotechn. 32:938–948. 2022. View Article : Google Scholar

9 

Wu Y, Chen T, Wu S, Huang Y and Li F: Knockdown of RFC3 enhances the sensitivity of colon cancer cells to oxaliplatin by inducing ferroptosis. Fund Clin Pharmacol. 39:e130442025. View Article : Google Scholar

10 

Liu L, Tao T, Liu S, Yang X, Chen X, Liang J, Hong R, Wang W, Yang Y, Li X, et al: An RFC4/Notch1 signaling feedback loop promotes NSCLC metastasis and stemness. Nat Commun. 12:26932021. View Article : Google Scholar

11 

Yang T, Fan Y, Bai G and Huang Y: RFC4 confers radioresistance of esophagus squamous cell carcinoma through regulating DNA damage response. Am J Physiol Cell Physiol. 328:C367–C380. 2025. View Article : Google Scholar

12 

Lee K and Park SH: Eukaryotic clamp loaders and unloaders in the maintenance of genome stability. Exp Mol Med. 52:1948–1958. 2020. View Article : Google Scholar

13 

Li T, Fu J, Zeng Z, Cohen D, Li J, Chen Q, Li B and Liu XS: TIMER2.0 for analysis of tumor-infiltrating immune cells. Nucleic Acids Res. 48:W509–W514. 2020. View Article : Google Scholar

14 

Mossi R and Hubscher U: Clamping down on clamps and clamp Loaders-the eukaryotic replication factor C. Eur J Biochem. 254:209–216. 1998. View Article : Google Scholar

15 

Virshup DM, Kauffman MG and Kelly TJ: Activation of SV40 DNA replication in vitro by cellular protein phosphatase 2A. EMBO J. 8:3891–3898. 1989. View Article : Google Scholar

16 

Virshup DM and Kelly TJ: Purification of replication protein C, a cellular protein involved in the initial stages of simian virus 40 DNA replication in vitro. Proc Natl Acad Sci USA. 86:3584–3588. 1989. View Article : Google Scholar

17 

Yoder BL and Burgers PM: Saccharomyces cerevisiae replication factor C. I. Purification and characterization of its ATPase activity. J Biol Chem. 266:22689–22697. 1991. View Article : Google Scholar

18 

Burbelo PD, Utani A, Pan ZQ and Yamada Y: Cloning of the large subunit of activator 1 (replication factor C) reveals homology with bacterial DNA ligases. Proc Natl Acad Sci USA. 90:11543–11547. 1993. View Article : Google Scholar

19 

Li X and Burgers PM: Cloning and characterization of the essential Saccharomyces cerevisiae RFC4 gene encoding the 37-kDa subunit of replication factor C. J Biol Chem. 269:21880–21884. 1994. View Article : Google Scholar

20 

Li X and Burgers PM: Molecular cloning and expression of the Saccharomyces cerevisiae RFC3 gene, an essential component of replication factor C. Proc Natl Acad Sci USA. 91:868–872. 1994. View Article : Google Scholar

21 

Noskov V, Maki S, Kawasaki Y, Leem SH, Ono B, Araki H, Pavlov Y and Sugino A: The RFC2 gene encoding a subunit of replication factor C of Saccharomyces cerevisiae. Nucleic Acids Res. 22:1527–1535. 1994. View Article : Google Scholar

22 

Podust VN, Georgaki A, Strack B and Hubscher U: Calf thymus RF-C as an essential component for DNA polymerase delta and epsilon holoenzymes function. Nucleic Acids Res. 20:4159–4165. 1992. View Article : Google Scholar

23 

Li Y, Gan S, Ren L, Yuan L, Liu J, Wang W, Wang X, Zhang Y, Jiang J, Zhang F and Qi X: Multifaceted regulation and functions of replication factor C family in human cancers. Am J Cancer Res. 8:1343–1355. 2018.

24 

Okumura K, Nogami M, Taguchi H, Dean FB, Chen M, Pan ZQ, Hurwitz J, Shiratori A, Murakami Y and Ozawa K: Assignment of the 36.5-kDa (RFC5), 37-kDa (RFC4), 38-kDa (RFC3), and 40-kDa (RFC2) subunit genes of human replication factor C to chromosome bands 12q24.2-q24.3, 3q27, 13q12.3-q13, and 7q11.23. Genomics. 25:274–278. 1995. View Article : Google Scholar

25 

Uhlmann F, Cai J, Gibbs E, O'Donnell M and Hurwitz J: Deletion analysis of the large subunit p140 in human replication factor C reveals regions required for complex formation and replication activities. J Biol Chem. 272:10058–10064. 1997. View Article : Google Scholar

26 

Cai J, Gibbs E, Uhlmann F, Phillips B, Yao N, O'Donnell M and Hurwitz J: A complex consisting of human replication Factor C p40, p37, and p36 subunits is a DNA-dependent ATPase and an intermediate in the assembly of the holoenzyme. J Biol Chem. 272:18974–18981. 1997. View Article : Google Scholar

27 

Cullmann G, Fien K, Kobayashi R and Stillman B: Characterization of the five replication factor C genes of Saccharomyces cerevisiae. Mol Cell Biol. 15:4661–4671. 1995. View Article : Google Scholar

28 

Tang Z, Kang B, Li C, Chen T and Zhang Z: GEPIA2: An enhanced web server for Large-scale expression profiling and interactive analysis. Nucleic Acids Res. 47:W556–W560. 2019. View Article : Google Scholar

29 

Delforge V, Tard C, Davion JB, Dujardin K, Wissocq A, Dhaenens CM, Mutez E and Huin V: RFC1: Motifs and phenotypes. Rev Neurol (Paris). 180:393–409. 2024. View Article : Google Scholar

30 

Giovannini S, Weller M, Hanzlíková H, Shiota T, Takeda S and Jiricny J: ATAD5 deficiency alters DNA damage metabolism and sensitizes cells to PARP inhibition. Nucleic Acids Res. 48:4928–4939. 2020. View Article : Google Scholar

31 

Fung LF, Lo AK, Yuen PW, Liu Y, Wang XH and Tsao SW: Differential gene expression in nasopharyngeal carcinoma cells. Life Sci. 67:923–936. 2000. View Article : Google Scholar

32 

Almalki E, Al-Amri A, Alrashed R, AL-Zharani M and Semlali A: The curcumin analog PAC is a potential solution for the treatment of Triple-negative breast cancer by modulating the gene expression of DNA repair pathways. Int J Mol Sci. 24:96492023. View Article : Google Scholar

33 

Moggs JG, Murphy TC, Lim FL, Moore DJ, Stuckey R, Antrobus K, Kimber I and Orphanides G: Anti-proliferative effect of estrogen in breast cancer cells that re-express ERalpha is mediated by aberrant regulation of cell cycle genes. J Mol Endocrinol. 34:535–551. 2005. View Article : Google Scholar

34 

Ji Z, Li J and Wang J: Up-regulated RFC2 predicts unfavorable progression in hepatocellular carcinoma. Hereditas. 158:172021. View Article : Google Scholar

35 

Oshima M, Takayama K, Yamada Y, Kimura N, Kume H, Fujimura T and Inoue S: Identification of DNA damage response-related genes as biomarkers for castration-resistant prostate cancer. Sci Rep. 13:196022023. View Article : Google Scholar

36 

Li G, Zhang P, Zhang W, Lei Z, He J, Meng J, Di T and Yan W: Identification of key genes and pathways in Ewing's sarcoma patients associated with metastasis and poor prognosis. Onco Targets Ther. 12:4153–4165. 2019. View Article : Google Scholar

37 

Koh JW and Park S: Knockdown of RFC2 prevents the proliferation, migration and invasion of cervical cancer cells. Anticancer Res. 45:989–1000. 2025. View Article : Google Scholar

38 

Avs KR, Pandi C, Kannan B, Pandi A, Jayaseelan VP and Arumugam P: RFC3 serves as a novel prognostic biomarker and target for head and neck squamous cell carcinoma. Clin Oral Invest. 27:6961–6969. 2023. View Article : Google Scholar

39 

Zhu J, Ye L, Sun S, Yuan J, Huang J and Zeng Z: Involvement of RFC3 in tamoxifen resistance in ER-positive breast cancer through the cell cycle. Aging. 15:13738–13752. 2023. View Article : Google Scholar

40 

Zhou J, Zhang W, Peng F, Sun J, He Z and Wu S: Downregulation of hsa_circ_0011946 suppresses the migration and invasion of the breast cancer cell line MCF-7 by targeting RFC3. Cancer Manag Res. 10:535–544. 2018. View Article : Google Scholar

41 

He Z, Wu S, Peng F, Zhang Q, Luo Y, Chen M and Bao Y: Up-Regulation of RFC3 promotes triple negative breast cancer metastasis and is associated with poor prognosis via EMT. Transl Oncol. 10:1–9. 2017. View Article : Google Scholar

42 

Gong S, Qu X, Yang S, Zhou S, Li P and Zhang Q: RFC3 induces epithelial-mesenchymal transition in lung adenocarcinoma cells through the Wnt/β-catenin pathway and possesses prognostic value in lung adenocarcinoma. Int J Mol Med. 44:2276–2288. 2019.

43 

Koh JW and Park S: RFC3 Knockdown decreases cervical cancer cell proliferation, migration and invasion. Cancer Genomics Proteomics. 22:127–135. 2024. View Article : Google Scholar

44 

Yu R, Wu X, Qian F and Yang Q: RFC3 drives the proliferation, migration, invasion and angiogenesis of colorectal cancer cells by binding KIF14. Exp Ther Med. 27:2222024. View Article : Google Scholar

45 

Yu L, Li J, Zhang M, Li Y, Bai J, Liu P, Yan J and Wang C: Identification of RFC4 as a potential biomarker for pan-cancer involving prognosis, tumour immune microenvironment and drugs. J Cell Mol Med. 28:e184782024. View Article : Google Scholar

46 

Guan S, Feng L, Wei J, Wang G and Wu L: Knockdown of RFC4 inhibits the cell proliferation of nasopharyngeal carcinoma in vitro and in vivo. Front Med. 17:132–142. 2023. View Article : Google Scholar

47 

You P, Wang D, Liu Z, Guan S, Xiao N, Chen H, Zhang X, Wu L, Wang G and Dong H: Knockdown of RFC 4 inhibits cell proliferation of oral squamous cell carcinoma in vitro and in vivo. FEBS Open Bio. 15:346–358. 2025. View Article : Google Scholar

48 

Wang J, Luo F, Huang T, Mei Y, Peng L, Qian C and Huang B: The upregulated expression of RFC4 and GMPS mediated by DNA copy number alteration is associated with the early diagnosis and immune escape of ESCC based on a bioinformatic analysis. Aging (Albany NY). 13:21758–21777. 2021. View Article : Google Scholar

49 

Zeng B, Liu X, Liu J, Qiu H, Zhang T, Chen X and Wang L: Roles of MARCKSL1, MCM6, RFC4, and PLAU genes in esophageal cancer and their association with radiotherapy response. Sci Rep. 15:235592025. View Article : Google Scholar

50 

Wang X, Yue X, Zhang R, Liu T, Pan Z, Yang M, Lu Z, Wang Z, Peng J, Le L, et al: Genome-wide RNAi screening identifies RFC4 as a factor that mediates radioresistance in colorectal cancer by facilitating nonhomologous end joining repair. Clin Cancer Res. 25:4567–4579. 2019. View Article : Google Scholar

51 

Xiang J, Fang L, Luo Y, Yang Z, Liao Y, Cui J, Huang M, Yang Z, Huang Y, Fan X, et al: Levels of human replication factor C4, a clamp loader, correlate with tumor progression and predict the prognosis for colorectal cancer. J Transl Med. 12:3202014. View Article : Google Scholar

52 

Arai M, Kondoh N, Imazeki N, Hada A, Hatsuse K, Matsubara O and Yamamoto M: The knockdown of endogenous replication factor C4 decreases the growth and enhances the chemosensitivity of hepatocellular carcinoma cells. Liver Int. 29:55–62. 2009. View Article : Google Scholar

53 

Erdogan E, Klee EW, Thompson EA and Fields AP: Meta-analysis of oncogenic protein kinase Ciota signaling in lung adenocarcinoma. Clin Cancer Res. 15:1527–1533. 2009. View Article : Google Scholar

54 

Zheng J, Lin N, Huang B, Wu M, Xiao L and Zeng B: Comprehensive analysis of RFC4 as a potential biomarker for regulating the immune microenvironment and predicting immune therapy response in lung adenocarcinoma. Front Immunol. 16:15782432025. View Article : Google Scholar

55 

Koh JW and Park S: Replication Factor C Subunit 4 plays a role in human breast cancer cell progression. Cancer Genomics Proteomics. 22:478–490. 2025. View Article : Google Scholar

56 

Zhu XY, Li PS, Qu H, Ai X, Zhao ZT and He JB: Replication factor C4, which is regulated by insulin-like growth factor 2 mRNA binding protein 2, enhances the radioresistance of breast cancer by promoting the stemness of tumor cells. Hum Cell. 38:652025. View Article : Google Scholar

57 

Huang B, Zheng J, Chen B, Wu M and Xiao L: Analysis of the correlation between RFC4 expression and tumor immune microenvironment and prognosis in patients with cervical cancer. Front Genet. 16:15143832025. View Article : Google Scholar

58 

Zhao X, Sun Y, Sun X, Li J, Shi X, Liang Z, Ma Y and Zhang X: AEG-1 Knockdown sensitizes glioma cells to radiation through impairing homologous recombination via targeting RFC5. DNA Cell Biol. 40:895–905. 2021. View Article : Google Scholar

59 

Martinez I, Wang J, Hobson KF, Ferris RL and Khan SA: Identification of differentially expressed genes in HPV-positive and HPV-negative oropharyngeal squamous cell carcinomas. Eur J Cancer. 43:415–432. 2007. View Article : Google Scholar

60 

Wang M, Xie T, Wu Y, Yin Q, Xie S, Yao Q, Xiong J and Zhang Q: Identification of RFC5 as a novel potential prognostic biomarker in lung cancer through bioinformatics analysis. Oncol Lett. 16:4201–4210. 2018.

61 

Xu S, Zhong F, Jiang J, Yao F, Li M, Tang M, Cheng Y, Yang Y, Wen W, Zhang X, et al: High Expression of SRSF10 promotes colorectal cancer progression by aberrant alternative splicing of RFC5. Technol Cancer Res. 23:153303382412719062024. View Article : Google Scholar

62 

Yao H, Zhou X, Zhou A, Chen J, Chen G, Shi X, Shi B, Tai Q, Mi X, Zhou G, et al: RFC5, regulated by circ_0038985/miR-3614-5p, functions as an oncogene in the progression of colorectal cancer. Mol Carcinog. 62:771–785. 2023. View Article : Google Scholar

63 

Li W, Wu D, Zhou Y, Zhang C and Liao X: Prognostic biomarker replication factor C subunit 5 and its correlation with immune infiltrates in acute myeloid leukemia. Hematology. 27:555–564. 2022. View Article : Google Scholar

64 

Zhang Y, Gao X, Yi J, Sang X, Dai Z, Tao Z, Wang M, Shen L, Jia Y, Xie D, et al: BTF3 confers oncogenic activity in prostate cancer through transcriptional upregulation of Replication Factor C. Cell Death Dis. 12:122021. View Article : Google Scholar

65 

Qiu X, Tan G, Wen H, Lian L and Xiao S: Forkhead box O1 targeting replication factor C subunit 2 expression promotes glioma temozolomide resistance and survival. Ann Transl Med. 9:6922021. View Article : Google Scholar

66 

Day M, Oliver AW and Pearl LH: Structure of the human RAD17-RFC clamp loader and 9-1-1 checkpoint clamp bound to a dsDNA-ssDNA junction. Nucleic Acids Res. 50:8279–8289. 2022. View Article : Google Scholar

67 

Niida H and Nakanishi M: DNA damage checkpoints in mammals. Mutagenesis. 21:3–9. 2006. View Article : Google Scholar

68 

Bermudez VP, Lindsey-Boltz LA, Cesare AJ, Maniwa Y, Griffith JD, Hurwitz J and Sancar A: Loading of the human 9-1-1 checkpoint complex onto DNA by the checkpoint clamp loader hRad17-replication factor C complex in vitro. Proc Natl Acad Sci USA. 100:1633–1638. 2003. View Article : Google Scholar

69 

Wang X, Zou L, Zheng H, Wei Q, Elledge SJ and Li L: Genomic instability and endoreduplication triggered by RAD17 deletion. Gene Dev. 17:965–970. 2003. View Article : Google Scholar

70 

Terret ME, Sherwood R, Rahman S, Qin J and Jallepalli PV: Cohesin acetylation speeds the replication fork. Nature. 462:231–234. 2009. View Article : Google Scholar

71 

Kim JT, Cho HJ, Park SY, Oh BM, Hwang YS, Baek KE, Lee YH, Kim HC and Lee HG: DNA replication and sister chromatid cohesion 1 (DSCC1) of the replication factor complex CTF18-RFC is critical for colon cancer cell growth. J Cancer. 10:6142–6153. 2019. View Article : Google Scholar

72 

Kang M, Ryu E, Lee S, Park J, Ha NY, Ra JS, Kim YJ, Kim J, Abdel-Rahman M, Park SH, et al: Regulation of PCNA cycling on replicating DNA by RFC and RFC-like complexes. Nat Commun. 10:24202019. View Article : Google Scholar

73 

Sikdar N, Banerjee S, Lee KY, Wincovitch S, Pak E, Nakanishi K, Jasin M, Dutra A and Myung K: DNA damage responses by human ELG1 in S phase are important to maintain genomic integrity. Cell Cycle. 8:3199–3207. 2009. View Article : Google Scholar

74 

Lee KY, Fu H, Aladjem MI and Myung K: ATAD5 regulates the lifespan of DNA replication factories by modulating PCNA level on the chromatin. J Cell Biol. 200:31–44. 2013. View Article : Google Scholar

75 

Szklarczyk D, Nastou K, Koutrouli M, Kirsch R, Mehryary F, Hachilif R, Hu D, Peluso ME, Huang Q, Fang T, et al: The STRING database in 2025: Protein networks with directionality of regulation. Nucleic Acids Res. 53:D730–D737. 2025. View Article : Google Scholar

76 

Hopfner KP and Hornung V: Molecular mechanisms and cellular functions of cGAS-STING signalling. Nat Rev Mol Cell Bio. 21:501–521. 2020. View Article : Google Scholar

77 

Yuan Q, Cai S, Chang Y, Zhang J, Wang M, Yang K and Jiang D: The multifaceted roles of mucins family in lung cancer: From prognostic biomarkers to promising targets. Front Immunol. 16:16081402025. View Article : Google Scholar

78 

Wu G, Zhou J, Zhu X, Tang X, Liu J, Zhou Q, Chen Z, Liu T, Wang W, Xiao X and Wu T: Integrative analysis of expression, prognostic significance and immune infiltration of RFC family genes in human sarcoma. Aging (Albany NY). 14:3705–3719. 2022. View Article : Google Scholar

79 

Deng J, Zhong F, Gu W and Qiu F: Exploration of prognostic biomarkers among replication factor C family in the hepatocellular carcinoma. Evol Bioinform. 17:11769343219941092021. View Article : Google Scholar

80 

Zhang J, Meng S, Wang X, Wang J, Fan X, Sun H, Ning R, Xiao B, Li X, Jia Y, et al: Sequential gene expression analysis of cervical malignant transformation identifies RFC4 as a novel diagnostic and prognostic biomarker. BMC Med. 20:4372022. View Article : Google Scholar

81 

Tu S, Zhang H, Yang X, Wen W, Song K, Yu X and Qu X: Screening of cervical cancer-related hub genes based on comprehensive bioinformatics analysis. Cancer Biomark. 32:303–315. 2021. View Article : Google Scholar

82 

Ho KH, Kuo TC, Lee YT, Chen PH, Shih CM, Cheng CH, Liu AJ, Lee CC and Chen KC: Xanthohumol regulates miR-4749-5p-inhibited RFC2 signaling in enhancing temozolomide cytotoxicity to glioblastoma. Life Sci. 254:1178072020. View Article : Google Scholar

83 

Alaa Eldeen M, Mamdouh F, Abdulsahib WK, Eid RA, Alhanshani AA, Shati AA, Alqahtani YA, Alshehri MA, Samir A, Zaki M, et al: Oncogenic potential of replication factor C subunit 4: Correlations with tumor progression and assessment of potential inhibitors. Pharmaceuticals (Basel). 17:1522024. View Article : Google Scholar

84 

Rohde JM, Rai G, Choi YJ, Sakamuru S, Fox JT, Huang R, Xia M, Myung K, Boxer MB and Maloney DJ: Discovery of ML367, inhibitor of ATAD5 stabilization. Probe Reports from the NIH Molecular Libraries Program [Internet] Bethesda (MD): National Center for Biotechnology Information (US); 2010

85 

Xu J, Wang G, Gong W, Guo S, Li D and Zhan Q: The noncoding function of NELFA mRNA promotes the development of oesophageal squamous cell carcinoma by regulating the Rad17-RFC2-5 complex. Mol Oncol. 14:611–624. 2020. View Article : Google Scholar

86 

Cortese A, Simone R, Sullivan R, Vandrovcova J, Tariq H, Yau WY, Humphrey J, Jaunmuktane Z, Sivakumar P, Polke J, et al: Biallelic expansion of an intronic repeat in RFC1 is a common cause of late-onsetataxia. Nat Genet. 51:649–658. 2019. View Article : Google Scholar

87 

Haffner MC, Zwart W, Roudier MP, True LD, Nelson WG, Epstein JI, De Marzo AM, Nelson PS and Yegnasubramanian S: Genomic and phenotypic heterogeneity in prostate cancer. Nat Rev Urol. 18:79–92. 2021. View Article : Google Scholar : PubMed/NCBI

88 

Huang S, Chen Y, Hu M, Fu S, Yao Z, He H, Wang L, Chen Z and Liu X: The role of the SIX family in cancer development and therapy: Insights from foundational and cutting-edge research. Crit Rev Oncol Hemat. 214:1048602025. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Luo D, Li B and Jiang X: Multiple roles of replication factor C family in pan‑cancer (Review). Oncol Rep 54: 165, 2025.
APA
Luo, D., Li, B., & Jiang, X. (2025). Multiple roles of replication factor C family in pan‑cancer (Review). Oncology Reports, 54, 165. https://doi.org/10.3892/or.2025.8998
MLA
Luo, D., Li, B., Jiang, X."Multiple roles of replication factor C family in pan‑cancer (Review)". Oncology Reports 54.6 (2025): 165.
Chicago
Luo, D., Li, B., Jiang, X."Multiple roles of replication factor C family in pan‑cancer (Review)". Oncology Reports 54, no. 6 (2025): 165. https://doi.org/10.3892/or.2025.8998
Copy and paste a formatted citation
x
Spandidos Publications style
Luo D, Li B and Jiang X: Multiple roles of replication factor C family in pan‑cancer (Review). Oncol Rep 54: 165, 2025.
APA
Luo, D., Li, B., & Jiang, X. (2025). Multiple roles of replication factor C family in pan‑cancer (Review). Oncology Reports, 54, 165. https://doi.org/10.3892/or.2025.8998
MLA
Luo, D., Li, B., Jiang, X."Multiple roles of replication factor C family in pan‑cancer (Review)". Oncology Reports 54.6 (2025): 165.
Chicago
Luo, D., Li, B., Jiang, X."Multiple roles of replication factor C family in pan‑cancer (Review)". Oncology Reports 54, no. 6 (2025): 165. https://doi.org/10.3892/or.2025.8998
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team