The noncoding function of NELFA mRNA promotes the development of oesophageal squamous cell carcinoma by regulating the Rad17‐RFC2‐5 complex

Xu, Jiancheng; Wang, Guangchao; Gong, Wei; Guo, Shichao; Li, Dan; Zhan, Qimin

doi:10.1002/1878-0261.12619

Cited by 3 publications

(2 citation statements)

References 45 publications

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“…RFC2, being the subunits of RFCs, located within the human chromosomal segments 7q11.23, plays a part in DNA replication repair and cell cycle checkpoint pathway (14,48). There were many studies about RFC2 and certain cancers, most of which stated that RFC2 was obviously upregulated in cancer tissues (19,28,52,53,54). Ho et al (27).…”

Section: Discussionmentioning

confidence: 99%

A Comprehensive Bioinformatic Analysis of RFC1/2/3/4/5 As Significant Clinical Indicators in The Diagnosis and Prognosis of Low-Grade Glioma

Wang

Huo

2021

Preprint

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Background: Replication factor C (RFC) proteins play a very important role in nuclear DNA replication, mismatch repair and cell cycle checkpoint pathways. However, the relationship between RFCs and brain tumors is still unclear, especially the diagnostic and prognostic significance of RFCs in low-grade glioma. Methods: In our study, we applied the Oncomine, GEPIA, Human Protein Atlas, cBioPortal, STRING, LinkedOmics and Tumor Immune Estimation Resource (TIMER) databases to analyze the transcriptional and survival data of RFCs in brain and central nervous system (CNS) cancer, especially in low-grade glioma.Results: We found that RFCs were highly expressed in brain and CNS cancer, including low-grade glioma. The transcriptional levels of RFCs were also associated with the tumor stages. Moreover, the survival analysis of RFCs in low-grade glioma patients revealed that enhanced expression of RFCs led to poorer prognosis. RFCs and their 50 frequently altered neighbor genes were found enriched in certain pathways. We also discovered the kinase targets, transcription factor targets and miRNA targets of RFCs in low-grade glioma. RFCs also showed positive correlation with certain infiltrated immune cells in low-grade glioma.Conclusions: These implied that RFCs are the possible biomarkers of the diagnosis and prognosis of low-grade glioma.

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Section: Discussionmentioning

confidence: 99%

A Comprehensive Bioinformatic Analysis of RFC1/2/3/4/5 As Significant Clinical Indicators in The Diagnosis and Prognosis of Low-Grade Glioma

Wang

Huo

2021

Preprint

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“…RFC2 plays an important role in the elongation of primed DNA templates by DNA polymerase δ and ε (18). Upregulated RFC2 expression has been associated with a number of cancers, such as nasopharyngeal (19) and esophageal squamous cell carcinoma (20). However, to the best of our knowledge, only a single study has reported the involvement of RFC2 in GBM, in which RFC2 was indicated to enhance temozolomide (TMZ) cytotoxicity (21).…”

Section: Microrna-744-5p Inhibits Glioblastoma Malignancy By Suppressing Replication Factor C Subunitmentioning

confidence: 99%

MicroRNA‑744‑5p inhibits glioblastoma malignancy by suppressing replication factor C subunit 2

et al. 2021

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Glioblastoma (GBM) is the most common malignant primary brain tumor, accounting for ~57% of all gliomas and 48% of all malignant primary central nervous system tumors in the United States. Abnormal expression of the replication factor C subunit 2 (RFC2) gene and microRNA (miR)-744-5p is associated with tumorigenic characteristics, including cellular proliferation, migration and invasiveness. However, the mechanism underlying the interaction between miR-744-5p and RFC2 in GBM remains unknown. Reverse transcription-quantitative (RT-q) PCR analysis of RFC2 and miR-744-5p was performed using GBM tumor tissues and cells, and the association between miR-744-5p and RFC2 was determined by dual-luciferase reporter assay. Cell Counting Kit 8, 5-bromo-2-deoxyuridine (BrdU), wound-healing and cellular adhesion assays, as well as the detection of caspase-3 activity and western blotting were used to detect cellular proliferation, migration and adhesion, caspase-3 activity, and Bax and Bcl-2 protein expression, respectively, in GBM cells. The results of the present study demonstrated that RFC2 expression was increased in GBM tissues and cell lines. Overexpression of RFC2 promoted cellular proliferation, migration, adhesion and an increase in Bcl-2 protein levels, and suppressed cellular caspase-3 activity and Bax protein expression, while silencing RFC2 resulted in the opposite effect. The effects of miR-744-5p inhibition were similar to those of RFC2 overexpression. Moreover, miR-744-5p was found to target RFC2 in GBM cells, and inhibiting the expression of RFC2 suppressed GBM tumorigenesis. In conclusion, the present study demonstrated that miR-744-5p targets RFC2 and suppresses the progression of GBM by repressing cellular proliferation, migration and Bcl-2 protein expression, and effectively promoting caspase-3 activity and Bax protein expression. These findings suggest a new target for the clinical treatment and improved prognosis of patients with GBM in the future.

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RFC2: a prognosis biomarker correlated with the immune signature in diffuse lower-grade gliomas

Zhao

Wang

et al. 2022

Sci Rep

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Diffuse lower-grade gliomas (LGG) represent the highly heterogeneous and infiltrative neoplasms in the central nervous system (CNS). Replication factor C 2 (RFC2) is a subunit of the RFC complex that modulates DNA replication and repair. However, the prognosis value of RFC2 and its association with the immune signature of tumor microenvironment (TME) in LGG remains unknown. Based on Oncomine, TCGA, GTEx, TIMER, GEPIA, and HPA databases, we evaluated RFC2 expression levels and its clinical prognostic value in LGG and other cancers. Then we analyzed the correlations between RFC2 expression and tumor mutation burden (TMB), tumor microsatellite instability (MSI), and mismatch repair (MMR) genes across cancers. And CIBERSORT and ESTIMATE algorithms were conducted to estimate the association of RFC2 with immune cell infiltration of LGG. Additionally, we performed the functional enrichment analyses of RFC2 in LGG. Then functional experiments were employed to further validate the oncogenic role of RFC2 in LGG. Our results showed that RFC2 was widely highly expressed in most types of cancer. And its expression was closely related to the clinicopathological features and prognosis in LGG and other cancer types. RFC2 levels were also correlated with TMB and MSI across various cancers. Furthermore, RFC2 was positively associated with the infiltration levels of immune cells and immune checkpoint genes in LGG. Additionally, in vitro experiments revealed that RFC2 played an oncogenic role in LGG progression. In conclusion, our findings revealed that RFC2 could serve as a reliable biomarker to predict the prognosis and immune signature for LGG.

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The noncoding function of NELFA mRNA promotes the development of oesophageal squamous cell carcinoma by regulating the Rad17‐RFC2‐5 complex

Cited by 3 publications

References 45 publications

A Comprehensive Bioinformatic Analysis of RFC1/2/3/4/5 As Significant Clinical Indicators in The Diagnosis and Prognosis of Low-Grade Glioma

A Comprehensive Bioinformatic Analysis of RFC1/2/3/4/5 As Significant Clinical Indicators in The Diagnosis and Prognosis of Low-Grade Glioma

MicroRNA‑744‑5p inhibits glioblastoma malignancy by suppressing replication factor C subunit 2

RFC2: a prognosis biomarker correlated with the immune signature in diffuse lower-grade gliomas

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