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Background  Human 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).    Methods  The 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.    Results   RFC4  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.    Conclusion   RFC4  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 material  The online version of this article (doi:10.1186/s12967-014-0320-0) contains supplementary material, which is available to authorized users.

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