Replication protein A: a reliable biologic marker of prognostic and therapeutic value in human astrocytic tumors

Kanakis, Dimitrios; Levidou, Georgia; Gakiopoulou, Hariklia; Eftichiadis, Christos; Thymara, Irene; Fragkou, Paraskevi C.; Trigka, Eleni Andriana; Boviatsis, Efstathios; Patsouris, Efstratios; Korkolopoulou, Penelope

doi:10.1016/j.humpath.2010.12.018

Cited by 13 publications

(15 citation statements)

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“…Expression of RPA1 is positively correlated with tumor grade and survival in patients with astrocytic tumors. 57 Higher expression of RPA1 is also linked to esophageal cancer and associated with lymph node metastasis. 58 Minichromosome maintenance protein 2 (MCM2) is a subunit of the hetero-hexameric DNA replication machinery, which is tightly regulated through cell cycle.…”

Section: Resultsmentioning

confidence: 99%

Identification of miR-145 targets through an integrated omics analysis

et al. 2015

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MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and protein synthesis. To characterize functions of miRNAs and to assess their potential applications, we carried out an integrated multi-omics analysis to study miR-145, a miRNA that has been shown to suppress tumor growth. We employed gene expression profiling, miRNA profiling and quantitative proteomic analysis of a pancreatic cancer cell line. In our transcriptomic analysis, overexpression of miR-145 was found to suppress the expression of genes that are implicated in development of cancer such as ITGA11 and MAGEA4 in addition to previously described targets such as FSCN1, YES1 and PODXL. Based on miRNA profiling, overexpression of miR-145 also upregulated other miRNAs including miR-124, miR-133b and miR-125a-3p, all of which are implicated in suppression of tumors and are generally co-regulated with miR-145 in other cancers. Using the SILAC system, we identified miR-145-induced downregulation of several oncoproteins/cancer biomarkers including SET, RPA1, MCM2, ABCC1, SPTBN1 and SPTLC1. Luciferase assay validation carried out on a subset of downregulated candidate targets confirmed them to be novel direct targets of miR-145. Overall, this multi-omics approach provided insights into miR-145-mediated tumor suppression and could be used as a general strategy to study the targets of individual miRNAs.

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Section: Resultsmentioning

confidence: 99%

Identification of miR-145 targets through an integrated omics analysis

et al. 2015

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“…The knowledge of the full-length structure of RPA would aid in a more complete understanding of the protein and perhaps assist in the design of more potent small molecule inhibitors. In addition to being a targeted by chemotherapeutic drugs, RPA has also been shown to be a prognostic indicator for patients with astrocytomas (Kanakis et al 2011 ) .…”

Section: Concluding Remarks: Future Research On Rpamentioning

confidence: 99%

The Structure and Function of Replication Protein A in DNA Replication

Prakash

Borgstahl

2012

Subcellular Biochemistry

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In all organisms from bacteria and archaea to eukarya, single-stranded DNA binding proteins play an essential role in most, if not all, nuclear metabolism involving single-stranded DNA (ssDNA). Replication protein A (RPA), the major eukaryotic ssDNA binding protein, has two important roles in DNA metabolism: (1) in binding ssDNA to protect it and to keep it unfolded, and (2) in coordinating the assembly and disassembly of numerous proteins and protein complexes during processes such as DNA replication. Since its discovery as a vital player in the process of replication, RPAs roles in recombination and DNA repair quickly became evident. This chapter summarizes the current understanding of RPA's roles in replication by reviewing the available structural data, DNA-binding properties, interactions with various replication proteins, and interactions with DNA repair proteins when DNA replication is stalled.

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“…Moreover, RPA2 was identified as an independent prognostic indicator of astrocytic tumors (6). In addition, decreased expression of both RPA1 and 2 resulted in an adverse prognosis for patients with muscle-invasive urothelial carcinoma and colon cancer (7,8).…”

Section: Introductionmentioning

confidence: 98%

“…Replication protein A (RPA) is a single-stranded DNA-binding gene family consisting of four members, RPA1-4 (4). RPAs play an essential role in DNA replication, repair, recombination and cell-cycle regulation (4)(5)(6)(7)(8). Previously, RPAs were thought to serve as prognostic biomarkers in several tumor types (5)(6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

“…RPAs play an essential role in DNA replication, repair, recombination and cell-cycle regulation (4)(5)(6)(7)(8). Previously, RPAs were thought to serve as prognostic biomarkers in several tumor types (5)(6)(7)(8). Specifically, high protein expression levels of RPA1 (detected using immunohistochemistry) were associated with poorer outcomes in patients with esophageal carcinoma, compared with those with normal levels of expression (5).…”

Section: Introductionmentioning

confidence: 99%

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Distinct expression and prognostic values of the replication protein A family in gastric cancer

Zhang

2020

Oncol Lett

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The replication protein A (RPA)1-4 family are single-stranded DNA-binding proteins that are essential components of DNA replication, repair and recombination, and cell cycle regulation. The present study aimed to evaluate the prognostic value of the RPA family members in patients with gastric cancer (GC), using datasets retrieved from the Oncomine public database. Datasets were retrieved for the purpose of comparing the RPA expression levels between GC and normal tissues. Additionally, Kaplan-Meier analysis was used to compare the overall survival (OS) times of GC patients that expressed different levels of RPA proteins. RPA1, 2, and 3 expression levels were all significantly upregulated in gastric intestinal-type, diffuse gastric, and gastric mixed adenocarcinomas, compared with those in normal mucosal tissues. Moreover, high mRNA expression levels of RPA3 and 4 predicted poorer OS times in all GCs, as well as patients with human epidermal growth factor receptor 2-negative and -positive GC. The high-risk group, separated by RPA signature, showed a poorer outcome than the low-risk group. RPA3 was the most strongly correlated with CD4+ T-cell levels. In conclusion, RPAs are novel prognostic indicators in GC, and can also predict the features of immunological diseases. Future experimental investigation into the roles of RPAs concerning the pathogenesis and development of GC may provide a novel biomarker or therapeutic target, improving the prognosis of patients with GC.Abbreviations: RPA, replication protein A; KM, Kaplan-Meier; OS, overall survival; HER2, human epidermal growth factor receptor 2; TIMER, tumor immune estimation response

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Replication protein A: a reliable biologic marker of prognostic and therapeutic value in human astrocytic tumors

Cited by 13 publications

References 30 publications

Identification of miR-145 targets through an integrated omics analysis

Identification of miR-145 targets through an integrated omics analysis

The Structure and Function of Replication Protein A in DNA Replication

Distinct expression and prognostic values of the replication protein A family in gastric cancer

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