Mutational and expressional analysis of RFC3, a clamp loader in DNA replication, in gastric and colorectal cancers

Kim, Yoo Ri; Song, Sang Yong; Kim, Sung Soo; An, Chang Hyeok; Lee, Sug Hyung; Yoo, Nam Jin

doi:10.1016/j.humpath.2010.03.006

Cited by 17 publications

(17 citation statements)

References 21 publications

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“…At previously, abundant researches have revealed that RFC played a pivotal role in DNA replication, DNA damage repair and checkpoint control [15], [16], [17]. In addition, the abnormal amplification of RFC gene has also been demonstrated to be involved in cancer cell proliferation.…”

Section: Introductionmentioning

confidence: 99%

Up-Regulation of RFC3 Promotes Triple Negative Breast Cancer Metastasis and is Associated With Poor Prognosis Via EMT

Peng

et al. 2017

Translational Oncology

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Triple-negative breast cancer (TNBC) was regarded as the most aggressive and mortal subtype of breast cancer (BC) since the molecular subtype system has been established. Abundant studies have revealed that epithelial-mesenchymal transition (EMT) played a pivotal role during breast cancer metastasis and progression, especially in TNBC. Herein, we showed that inhibition the expression of replication factor C subunit 3 (RFC3) significantly attenuated TNBC metastasis and progression, which was associated with EMT signal pathway. In TNBC cells, knockdown of RFC3 can down-regulate mesenchymal markers and up-regulate epithelial markers, significantly attenuated cell proliferation, migration and invasion. Additionally, silencing RFC3 expression can decrease nude mice tumor volume, weight and relieve lung metastasis in vivo. Furthermore, we also demonstrated that overexpression of RFC3 in TNBC showed increased metastasis, progression and poor prognosis. We confirmed all of these results by immunohistochemistry analysis in 127 human TNBC tissues and found that RFC3 expression was significantly associated with poor prognosis in TNBC. Taken all these findings into consideration, we can conclude that up-regulation of RFC3 promotes TNBC progression through EMT signal pathway. Therefore, RFC3 could be an independent prognostic factor and therapeutic target for TNBC.

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Section: Introductionmentioning

confidence: 99%

Up-Regulation of RFC3 Promotes Triple Negative Breast Cancer Metastasis and is Associated With Poor Prognosis Via EMT

Peng

et al. 2017

Translational Oncology

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“…Of interest, RFC1 , RFC2 and RFC4 were significantly downregulated (nominal p value <0.05) in nasal epithelium as well; however, only RFC1 was also significantly downregulated in bronchial epithelium. Downregulation of RFC3 has been associated with lung-, gastric- and colorectal cancer [ 42 , 43 ], but it might also play a role in COPD as oxidative stress due to cigarette smoke induces DNA damage.…”

Section: Discussionmentioning

confidence: 99%

Nasal gene expression differentiates COPD from controls and overlaps bronchial gene expression

et al. 2017

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BackgroundNasal gene expression profiling is a promising method to characterize COPD non-invasively. We aimed to identify a nasal gene expression profile to distinguish COPD patients from healthy controls. We investigated whether this COPD-associated gene expression profile in nasal epithelium is comparable with the profile observed in bronchial epithelium.MethodsGenome wide gene expression analysis was performed on nasal epithelial brushes of 31 severe COPD patients and 22 controls, all current smokers, using Affymetrix Human Gene 1.0 ST Arrays. We repeated the gene expression analysis on bronchial epithelial brushes in 2 independent cohorts of mild-to-moderate COPD patients and controls.ResultsIn nasal epithelium, 135 genes were significantly differentially expressed between severe COPD patients and controls, 21 being up- and 114 downregulated in COPD (false discovery rate < 0.01). Gene Set Enrichment Analysis (GSEA) showed significant concordant enrichment of COPD-associated nasal and bronchial gene expression in both independent cohorts (FDRGSEA < 0.001).ConclusionWe identified a nasal gene expression profile that differentiates severe COPD patients from controls. Of interest, part of the nasal gene expression changes in COPD mimics differentially expressed genes in the bronchus. These findings indicate that nasal gene expression profiling is potentially useful as a non-invasive biomarker in COPD.Trial registration ClinicalTrials.gov registration number NCT01351792 (registration date May 10, 2011), ClinicalTrials.gov registration number NCT00848406 (registration date February 19, 2009), ClinicalTrials.gov registration number NCT00807469 (registration date December 11, 2008).Electronic supplementary materialThe online version of this article (10.1186/s12931-017-0696-5) contains supplementary material, which is available to authorized users.

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“…Thus, there is abundant evidence implicating replication factor C genes in tumorigenesis and our study has identified a novel cancer-promoting role for factor C3 in EAC. Interestingly, a recent study reported frequent loss of function mutations and down-regulation of RFC3 in gastric and colorectal cancers (46). The findings of this study and ours suggest RFC3 may act in a tissue specific manner in the context of cancer.…”

Section: Discussionmentioning

confidence: 99%

Integrative Genomics Identified RFC3 As an Amplified Candidate Oncogene in Esophageal Adenocarcinoma

Lockwood

Thu

Lin

et al. 2012

Clinical Cancer Research

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Purpose Esophageal adenocarcinoma (EAC) is a lethal malignancy that can develop from the premalignant condition, Barrett’s esophagus (BE). Currently, there are no validated simple methods to predict which patients will progress to EAC. A better understanding of the genetic mechanisms driving EAC tumorigenesis is needed to identify new therapeutic targets and develop biomarkers capable of identifying high-risk patients that would benefit from aggressive neoadjuvant therapy. We employed an integrative genomics approach to identify novel genes involved in EAC biology that may serve as useful clinical markers. Experimental Design Whole genome tiling-path array CGH was used to identify significant regions of copy number (CN) alteration in 20 EACs and 10 matching BE tissues. CN and gene expression data were integrated to identify candidate oncogenes within regions of amplification and multiple additional sample cohorts were assessed to validate candidate genes. Results We identified RFC3 as a novel, candidate oncogene activated by amplification in ~25% of EAC samples. RFC3 was also amplified in BE from a patient whose EAC harbored amplification, and was differentially expressed between non-malignant and EAC tissues. CN gains were detected in other cancer types and RFC3 knockdown inhibited proliferation and anchorage-independent growth of cancer cells with increased CN, but had little effect on those without. Moreover, high RFC3 expression was associated with poor patient outcome in multiple cancer types. Conclusions RFC3 is a candidate oncogene amplified in EAC. RFC3 DNA amplification is also prevalent in other epithelial cancer types and RFC3 expression could serve as a prognostic marker.

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Mutational and expressional analysis of RFC3, a clamp loader in DNA replication, in gastric and colorectal cancers

Cited by 17 publications

References 21 publications

Up-Regulation of RFC3 Promotes Triple Negative Breast Cancer Metastasis and is Associated With Poor Prognosis Via EMT

Up-Regulation of RFC3 Promotes Triple Negative Breast Cancer Metastasis and is Associated With Poor Prognosis Via EMT

Nasal gene expression differentiates COPD from controls and overlaps bronchial gene expression

Integrative Genomics Identified RFC3 As an Amplified Candidate Oncogene in Esophageal Adenocarcinoma

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