Overexpression of RRM2 decreases thrombspondin-1 and increases VEGF production in human cancer cells in vitro and in vivo: implication of RRM2 in angiogenesis

Zhang, Keqiang; Hu, Shuya; Wu, Jun; Chen, Linling; Lü, Jianming; Wang, Xiaochen; Liu, Xiyong; Zhou, Bingsen; Yen, Yun

doi:10.1186/1476-4598-8-11

Cited by 90 publications

(89 citation statements)

References 33 publications

(62 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As we all know, relationships of annotation terms in one cluster have similar annotation contents and correlative functions. Some researchers indicated that overexpression of RRM2 significantly enhances the invasive and metastatic potential of tumor [1,32]. Therefore, we deduced the weaker RRM2 phosphoprotein function in HCC consistent with our above computation.…”

Section: Discussionsupporting

confidence: 75%

<i>RRM2</i> Computational Phosphoprotein Network Construction and Analysis between No-Tumor Hepatitis/Cirrhotic Liver Tissues and Human Hepatocellular Carcinoma (HCC)

Wang

Huang

Jiang

2010

Cell Physiol Biochem

View full text Add to dashboard Cite

RRM2 computational phosphoprotein network construction and analysis of human hepatocellular carcinoma (HCC) is very useful to identify novel markers and potential targets for prognosis and therapy. By integration of gene regulatory network infer (GRNInfer) and the database for annotation, visualization and integrated discovery (DAVID) we identified and constructed significant molecule RRM2 phosphoprotein network from 25 no-tumor hepatitis/cirrhotic liver tissues and 25 HCC patients in the same GEO Dataset GSE10140-10141. We gained the negative result of RRM2 phosphoprotein module through the net numbers of activation minus inhibition compared with no-tumor hepatitis/cirrhotic liver tissues and predicted possibly the decrease of RRM2 phosphoprotein module in HCC. Our integrative result showed that RRM2 phosphoprotein cluster of HCC contained both in human no-tumor hepatitis/cirrhotic liver tissues and HCC terms of phosphoprotein (with RRM2) and cell cycle (without RRM2), only in HCC terms of cell-cell signaling, cell projection part, glycoprotein, cell projection, cell adhesion, biological adhesion, integral to plasma membrane, plasma membrane, kinase and phosphorus metabolic process (without RRM2), and none in HCC terms of cell death (without RRM2) and ion binding (with RRM2) compared with human no-tumor hepatitis/cirrhotic liver tissues, all the condition is vital to invasion of HCC. Therefore, we deduced the weaker RRM2 phosphoprotein function in HCC consistent with our above computation. It would be necessary of RRM2 phosphoprotein function decrease to invasion of HCC. RRM2 phosphoprotein interaction module construction in HCC can be a new route for studying the pathogenesis of HCC.

show abstract

Section: Discussionsupporting

confidence: 75%

<i>RRM2</i> Computational Phosphoprotein Network Construction and Analysis between No-Tumor Hepatitis/Cirrhotic Liver Tissues and Human Hepatocellular Carcinoma (HCC)

Wang

Huang

Jiang

2010

Cell Physiol Biochem

View full text Add to dashboard Cite

show abstract

“…Although only three patients were assigned to the PR molecular subtype, the hazard for TTT was 9-fold the average, identifying a subset of patients with imminent progression, as also reported by Hose et al 32 The top gene in the GEP4 model, RRM2, is the beta subunit of ribonucleotide reductase (RNR). RRM2 overexpression is associated with cellular invasiveness, metastasis and tumor angiogenesis 33 via activation of the ERK1/2 signaling pathway 34 in cancer. RRM2 expression independently identified 15.2% patients with a 2-year TTT estimate of 75% (Online Supplementary Figure S1).…”

Section: Discussionmentioning

confidence: 99%

Four genes predict high risk of progression from smoldering to symptomatic multiple myeloma (SWOG S0120)

et al. 2015

View full text Add to dashboard Cite

© F e r r a t a S t o r t i F o u n d a t i o nGenomics of high-risk SMM haematologica | 2015; 100(9) 1215 Methods Eligibility criteria and study designPatients with SMM seen at the Myeloma Institute for Research and Therapy were included in a prospective, observational clinical trial (SWOG S0120) as part of a national cooperative group trial to identify biological correlates that may relate to progression to symptomatic disease. Other eligibility criteria included no prior therapy for the plasma cell disorder and willingness to submit samples for research. Diagnostic criteria for SMM were based on the International Myeloma Working Group convention.3 All patients signed informed consent, in keeping with the Declaration of Helsinki and federal and institutional guidelines. The protocol was approved by the National Cancer Institute and all participating centers' internal review boards.All patients underwent detailed clinical staging at initial registration, including full blood count, analysis of blood chemistry, and standard MM-related serological and urinary measurements. Nephelometric analysis was performed to determine serum immunoglobulin levels. Immunofixation analyses of serum and urine were performed to define the nature of the monoclonal protein present in serum and/or urine. Bone marrow aspirates and biopsies were obtained for cytological and histopathological evaluation of the degree of plasma cell infiltration, including immunohistochemical clonality assessment. Metaphase karyotyping was performed on at least 20 Giemsa-stained metaphases. 23 In most patients, serum FLC assays were used to quantify k and l light chains. Imaging studies involved standard metastatic bone surveys by X-ray examination, and, when possible, MRI of the entire spine was used to identify focal lesions. The minimum follow-up of patients involved MM-related laboratory studies at 3, 6, and 12 months in the first year, and then every 6 to 12 months. Gene expression profiling and statistical methodsA sample of bone marrow aspirate was collected to isolate CD138 + plasma cells with immunomagnetic bead selection (autoMACS; Miltenyi Biotec) as described elsewhere. 24 The purity of the plasma cells was monitored by flow cytometry and >85% purity was used as a criterion for inclusion of GEP data. Total RNA from these plasma cells was used for the GEP with Affymetrix U133 Plus 2.0 microarrays. We identified patients with SMM and baseline GEP data who were cared for at this institution. We evaluated 54,675 Affymetrix gene probes for their potential to predict time to myeloma therapy (TTT). Probes were ranked by their qvalues; 25 we used 10-fold cross validation to identify the number of genes at the top of this list, which collectively maximized the concordance between risk score and survival. Gene scores were computed by subtracting the sum of the expressions of the up-regulated probes from the sum of the expressions of the down-regulated probes, then dividing by the total number of probes. A running log-rank test was used to iden...

show abstract

“…20 Overexpression of RRM2 has been associated with increased invasion, angiogenesis, and metastasis. 21 In addition, overexpression of RRM2 in pancreatic adenocarcinoma has been found to induce MMP9, 22 which demonstrated a 3.33-fold increase in expression in tumor-adjacent compared with distant adipose tissue. Increased levels of MMP9 have been found on M2 macrophages and are induced in promonocytes when co-cultured with breast cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Gene expression differences in adipose tissue associated with breast tumorigenesis

et al. 2014

View full text Add to dashboard Cite

Overexpression of RRM2 decreases thrombspondin-1 and increases VEGF production in human cancer cells in vitro and in vivo: implication of RRM2 in angiogenesis

Cited by 90 publications

References 33 publications

<i>RRM2</i> Computational Phosphoprotein Network Construction and Analysis between No-Tumor Hepatitis/Cirrhotic Liver Tissues and Human Hepatocellular Carcinoma (HCC)

<i>RRM2</i> Computational Phosphoprotein Network Construction and Analysis between No-Tumor Hepatitis/Cirrhotic Liver Tissues and Human Hepatocellular Carcinoma (HCC)

Four genes predict high risk of progression from smoldering to symptomatic multiple myeloma (SWOG S0120)

Gene expression differences in adipose tissue associated with breast tumorigenesis

Contact Info

Product

Resources

About