The Expression of Ribonucleotide Reductase M2 in the Carcinogenesis of Uterine Cervix and Its Relationship with Clinicopathological Characteristics and Prognosis of Cancer Patients

Su, Ying; Wu, Tzu Fan; Ko, Jiunn‐Liang; Tsai, Hsiu Ting; Tee, Yi Torng; Chien, Ming Hsien; Chou, Chi; Lin, Wea Lung; Low, Hui Ying; Chou, Ming‐Yung; Yang, Shun Fa; Wang, Po Hui

doi:10.1371/journal.pone.0091644

Cited by 22 publications

(21 citation statements)

References 37 publications

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“…For example, RRM2 may act as a prognostic marker for breast cancer and for tamoxifen resistance [ Putluri et al, 2014 ]. RRM2 may also serve as marker for cervical cancer, with its overexpression correlating with higher grade cancers and predicting poor survival [ Su et al, 2014 ]. Another study implicated RRM2 in promoting angiogenesis in cervical tumors [ Wang et al, 2014 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of Potential Glucocorticoid Receptor Therapeutic Targets in Multiple Myeloma

et al. 2015

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Glucocorticoids (GC) are a cornerstone of combination therapies for multiple myeloma. However, patients ultimately develop resistance to GCs frequently based on decreased glucocorticoid receptor (GR) expression. An understanding of the direct targets of GC actions, which induce cell death, is expected to culminate in potential therapeutic strategies for inducing cell death by regulating downstream targets in the absence of a functional GR. The specific goal of our research is to identify primary GR targets that contribute to GC-induced cell death, with the ultimate goal of developing novel therapeutics around these targets that can be used to overcome resistance to GCs in the absence of GR. Using the MM.1S glucocorticoid-sensitive human myeloma cell line, we began with the broad platform of gene expression profiling to identify glucocorticoid-regulated genes further refined by combination treatment with phosphatidylinositol-3’-kinase inhibition (PI3Ki). To further refine the search to distinguish direct and indirect targets of GR that respond to the combination GC and PI3Ki treatment of MM.1S cells, we integrated 1) gene expression profiles of combination GC treatment with PI3Ki, which induces synergistic cell death; 2) negative correlation between genes inhibited by combination treatment in MM.1S cells and genes over-expressed in myeloma patients to establish clinical relevance and 3) GR chromatin immunoprecipitation with massively parallel sequencing (ChIP-Seq) in myeloma cells to identify global chromatin binding for the glucocorticoid receptor (GR). Using established bioinformatics platforms, we have integrated these data sets to identify a subset of candidate genes that may form the basis for a comprehensive picture of glucocorticoid actions in multiple myeloma. As a proof of principle, we have verified two targets, namely RRM2 and BCL2L1, as primary functional targets of GR involved in GC-induced cell death.

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Section: Discussionmentioning

confidence: 99%

Identification of Potential Glucocorticoid Receptor Therapeutic Targets in Multiple Myeloma

et al. 2015

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“…RRM2 is often overexpressed in many kinds of cancers, such as colorectal cancer, non-small cell lung cancer (NSCLC), breast cancer, bladder cancer, ovarian cancer, pancreatic cancer, head and neck cancer and lung cancer [12][13][14][15][16]. RRM2 also can be considered as a prognostic marker for cancers including NSCLC, cervical cancer, and pancreatic cancer [17][18][19]. Additionally, RRM2 is associated with chemo-resistance during cancer treatment.…”

Section: Discussionmentioning

confidence: 99%

“…1A. It has been demonstrated that high RRM2 expression is an indicator of poor prognosis in many types of cancer [17][18][19][33][34][35]. Here, we analyzed the relationship between RRM2 expression and the survival of GBM patients.…”

Section: Rrm2 Expression Is Enhanced In Human Glioma Tissuesmentioning

confidence: 99%

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RRM2 is a potential prognostic biomarker with functional significance in glioma

Sun¹,

Yang²,

Zhang³

et al. 2019

Int. J. Biol. Sci.

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Glioma is one of the most common brain tumors, suggesting the importance of investigating the molecular mechanism of gliomas. We studied the roles of Ribonucleotide Reductase Regulatory Subunit M2 (RRM2) in glioma. Expressions of RRM2 are higher in glioma tissues evidenced by TCGA data, western blot and immunohistochemistry. RRM2 is negatively correlated with glioma patient's survival. RNA-seq showed that genes involved in apoptosis, proliferation, cell adhesion and negative regulation of signaling were up-regulated upon RNAi-mediated knock-down of RRM2. Cell phenotypes specific for stably knocking down RRM2 were determined using stable transfection in vitro. In an in vivo model, knock-down of RRM2 inhibited tumor growth and caused suppression of AKT and ERK1/2 signalings. Interfering RRM2 also down-regulated the expression of cyclin A, cyclin B1, cyclin D1, Vimentin, and N-cadherin, and elevated E-cadherin expression. Moreover, overexpression of RRM2 failed to increase the expression of cyclin B1, cyclin D1, and N-cadherin when phosphorylation of AKT and ERK1/2 was suppressed by LY294002 or PD98059. These findings indicated that RRM2 is a positive regulator of glioma progression which contributes to the migration and proliferation of glioma cells through ERK1/2 and AKT signalings and might be a novel prognostic indicator for glioma patients.

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“…The destruction of the cancer cells by cisplatin requires binding of the drug to DNA and the formation of platinum-DNA adducts, which may establish inter-and intra-strand DNA crosslinks, thereby inhibiting DNA replication (Su et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Influence of Morinda citrifolia (Noni) on Expression of DNA Repair Genes in Cervical Cancer Cells

Gupta

Bajpai²,

Singh³

2015

Asian Pacific Journal of Cancer Prevention

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Background: Previous studies have suggested that Morinda citrifolia (Noni) has potential to reduce cancer risk. Objective: The purpose of this study was to investigate the effect of Noni, cisplatin, and their combination on DNA repair genes in the SiHa cervical cancer cell line. Materials and Methods: SiHa cells were cultured and treated with 10% Noni, 10 µg/dl cisplatin or their combination for 24 hours. Post culturing, the cells were pelleted, RNA extracted, and processed for investigating DNA repair genes by real time PCR. Results: The expression of nucleotide excision repair genes ERCC1, ERCC2, and ERCC4 and base excision repair gene XRCC1 was increased 4 fold, 8.9 fold, 4 fold, and 5.5 fold, respectively, on treatment with Noni as compared to untreated controls (p<0.05). In contrast, expression was found to be decreased 22 fold, 13 fold, 16 fold, and 23 fold on treatment with cisplatin (p<0.05). However, the combination of Noni and cisplatin led to an increase of 2 fold, 1.6 fold, 3 fold, 1.2 fold, respectively (p<0.05). Conclusions: Noni enhanced the expression of DNA repair genes by itself and in combination with cisplatin. However, high expression of DNA repair genes at mRNA level only signifies efficient DNA transcription of the above mentioned genes; further investigations are needed to evaluate the DNA repair protein expression.

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The Expression of Ribonucleotide Reductase M2 in the Carcinogenesis of Uterine Cervix and Its Relationship with Clinicopathological Characteristics and Prognosis of Cancer Patients

Cited by 22 publications

References 37 publications

Identification of Potential Glucocorticoid Receptor Therapeutic Targets in Multiple Myeloma

Identification of Potential Glucocorticoid Receptor Therapeutic Targets in Multiple Myeloma

RRM2 is a potential prognostic biomarker with functional significance in glioma

Influence of Morinda citrifolia (Noni) on Expression of DNA Repair Genes in Cervical Cancer Cells

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