Levels of human replication factor C4, a clamp loader, correlate with tumor progression and predict the prognosis for colorectal cancer

Abstract

BackgroundHuman replication factor C4 (RFC4) is involved in DNA replication as a clamp loader and is aberrantly regulated across a range of cancers. The current study aimed to investigate the function of RFC4 in colorectal cancer (CRC).MethodsThe mRNA levels of RFC4 were assessed in 30 paired primary CRC tissues and matched normal colonic tissues by quantitative PCR. The protein expression levels of RFC4 were evaluated by western blotting (n = 16) and immunohistochemistry (IHC; n = 49), respectively. Clinicopathological features and survival data were correlated with the expression of RFC4 by IHC analysis in a tissue microarray comprising 331 surgically resected CRC. The impact of RFC4 on cell proliferation and the cell cycle was assessed using CRC cell lines.ResultsRFC4 expression was significantly increased in CRC specimens as compared to adjacent normal colonic tissues (P <0.05). High levels of RFC4, determined on a tissue microarray, were significantly associated with differentiation, an advanced stage by the Tumor-Node-Metastasis (TNM) staging system, and a poor prognosis, as compared to low levels of expression (P <0.05). However, in multivariate analysis, RFC4 was not an independent predictor of poor survival for CRC. In vitro studies, the loss of RFC4 suppressed CRC cell proliferation and induced S-phase cell cycle arrest.ConclusionRFC4 is frequently overexpressed in CRC, and is associated with tumor progression and worse survival outcome. This might be attributed to the regulation of CRC cell proliferation and cell cycle arrest by RFC4.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-014-0320-0) contains supplementary material, which is available to authorized users.

Identifying Tumorigenesis and Prognosis-Related Genes of Lung Adenocarcinoma: Based on Weighted Gene Coexpression Network Analysis

“…Similar to RACGAP1, RFC4 (also known as human replication factor C4) participates in the regulation of cell cycle as well, which acts as a clamp loader in DNA replication. Previous studies showed that the high expression of RFC4 was the biomarker of tumorigenesis, poor survival [41], as well as chemotherapy resistance of colorectal cancer patients [42]. Given no experimental results supporting the role of RFC4 in LUAD, further investigation is needed.…”

Identification of Core Gene Expression Signature and Key Pathways in Colorectal Cancer

“…Jun Xiang et al's results revealed that the overexpression of RFC4 commonly occurs in CRC and that a high expression level of RFC4 is associated with poor differentiation and late TNM stages in patients with CRC. Higher levels of RFC4 protein expression correlate with a worse overall survival in CRC (Xiang et al, 2014). Human pituitary tumor transforming gene-1 (PTTG1) is a novel oncogene.…”

Common and distinct features of potentially predictive biomarkers in small cell lung carcinoma and large cell neuroendocrine carcinoma of the lung by systematic and integrated analysis

“…RFC4 is a member of the RFC family and has been found to be involved in DNA replication (Arai et al, ). In colorectal cancer, the forced expression of RFC4 was associated with tumor progression, poor prognosis (Xiang et al, ), and radioresistance (X. C. Wang, Yue, et al, ). RFC4 knockdown in liver cancer cells could suppress proliferation and induce apoptosis (Arai et al, ).…”

“…AURKA hsa-miR-25-3p hsa-miR-92a-3p hsa-miR-363-3p hsa-miR-367-3p hsa-miR-490-3p hsa-miR-92b-3p hsa-miR-421 hsa-miR-32-5p with tumor progression, poor prognosis (Xiang et al, 2014), and radioresistance (X. C. Wang, Yue, et al, 2019). RFC4 knockdown in liver cancer cells could suppress proliferation and induce apoptosis (Arai et al, 2009).…”