MCM3: A Novel Proliferation Marker in Oral Squamous Cell Carcinoma

Valverde, Ludmila de Faro; Freitas, Roseli Santos de; Pereira, Telma Ruth; Resende, Marina França de; Agra, Ivan Marcelo Gonçalves; Santos, Jean Nunes dos; Reis, Mitermayer Galvão dos; Sales, Caroline Brandi Schlaepfer; Rocha, Clarissa Araújo Gurgel

doi:10.1097/pai.0000000000000397

Cited by 32 publications

(35 citation statements)

References 35 publications

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“…Some subunits have been studied in HCC, for example, MCM7 is a poor prognostic factor for HCC and promotes HCC growth through activating MAPK signaling [9], MCM6 is a novel serum biomarker for early HCC and promotes HCC metastasis through activating MEK/ERK pathway [10]. MCM3 belongs to MCM2–7 complex, it is a poor prognosis marker for oral squamous cell carcinoma, melanoma, papillary thyroid carcinoma, cutaneous T-cell lymphomas, osteosarcoma, glioma, keratocystic odontogenic tumor, anaplastic astrocytoma and salivary gland epithelial tumors [11–20]. MCM3 is upregulated in prostate cancer tissues samples with bone metastasis, mouse model showed that MCM3 is increased in mesenchymal-derived tumors [21].…”

Section: Introductionmentioning

confidence: 99%

Minichromosome maintenance 3 promotes hepatocellular carcinoma radioresistance by activating the NF-κB pathway

Yang

Xie

Tang

et al. 2019

J Exp Clin Cancer Res

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Background Hepatocellular carcinoma (HCC) is the most common tumors in the worldwide, it develops resistance to radiotherapy during treatment, understanding the regulatory mechanisms of radioresistance generation is the urgent need for HCC therapy. Methods qRT-PCR, western blot and immunohistochemistry were used to examine MCM3 expression. MTT assay, colony formation assay, terminal deoxynucleotidyl transferase nick end labeling assay and In vivo xenograft assay were used to determine the effect of MCM3 on radioresistance . Gene set enrichment analysis, luciferase reporter assay, western blot and qRT-PCR were used to examine the effect of MCM3 on NF-κB pathway. Results We found DNA replication initiation protein Minichromosome Maintenance 3 (MCM3) was upregulated in HCC tissues and cells, patients with high MCM3 expression had poor outcome, it was an independent prognostic factor for HCC. Cells with high MCM3 expression or MCM3 overexpression increased the radioresistance determined by MTT assay, colony formation assay, TUNEL assay and orthotopic transplantation mouse model, while cells with low MCM3 expression or MCM3 knockdown reduced the radioresistance. Mechanism analysis showed MCM3 activated NF-κB pathway, characterized by increasing the nuclear translocation of p65, the expression of the downstream genes NF-κB pathway and the phosphorylation of IKK-β and IκBα. Inhibition of NF-κB in MCM3 overexpressing cells using small molecular inhibitor reduced the radioresistance, suggesting MCM3 increased radioresistance through activating NF-κB pathway. Moreover, we found MCM3 expression positively correlated with NF-κB pathway in clinic. Conclusions Our findings revealed that MCM3 promoted radioresistance through activating NF-κB pathway, strengthening the role of MCM subunits in the tumor progression and providing a new target for HCC therapy. Electronic supplementary material The online version of this article (10.1186/s13046-019-1241-9) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Minichromosome maintenance 3 promotes hepatocellular carcinoma radioresistance by activating the NF-κB pathway

Yang

Xie

Tang

et al. 2019

J Exp Clin Cancer Res

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“…[28][29][30][31] Current efforts increasingly focus on molecular biomarkers, which may make the histologic classification of tumours more accurate and facilitate us in identifying more aggressive cancers, promoting staging revisions, and creating personalized therapy and better clinical outcomes. [32][33][34][35][36] The goal of this study was to identify the prognostic value of certain clotting markers for patients with colorectal cancer.…”

Section: Discussionmentioning

confidence: 99%

<p>Prediction of Poor Outcomes in Patients with Colorectal Cancer: Elevated Preoperative Prothrombin Time (PT) and Activated Partial Thromboplastin Time (APTT)</p>

Zhang¹,

Ye²,

Luo³

et al. 2020

CMAR

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Background and Objective: Tools for the non-invasive assessment of colorectal cancer (CRC) prognosis have profound significance. Although plasma coagulation tests have been investigated in a variety of tumours, the prognostic value of the prothrombin time (PT) and activated partial thromboplastin time (APTT) in CRC has not been discussed. Our study objective was to explore the prognostic significance of preoperative PT and APTT in CRC patients. Patients and Methods: A retrospective analysis of preoperative coagulation indexes including PT, PTA, INR, APTT, FIB, TT, PLT, NLR and PLR in 250 patients with CRC was performed. Kaplan-Meier and multivariate Cox regression analysis were used to demonstrate the prognostic value of these preoperative coagulation indexes. Results: The overall survival (OS, p<0.05) and disease-free survival (DFS, p<0.05) of CRC patients with lower PT and APTT levels were significantly prolonged. Based on univariate analysis, PT levels (p<0.001, p<0.001), PTA levels (p=0.001, p=0.001), APTT levels (p=0.001, p<0.001), INR levels (p<0.001, p<0.001), fibrinogen levels (p=0.032, p=0.036), tumour status (p=0.005, p=0.003), nodal status (p<0.001, p<0.001), metastasis status (p<0.001, p<0.001) and TNM stages (p<0.001, p<0.001) were remarkably associated with DFS and OS. Multivariate Cox regression analysis suggested that the levels of PT (HR: 2.699, p=0.006) and APTT (HR: 1.942, p=0.015), metastasis status (HR: 2.091, p= 0.015) and TNM stage (HR: 7.086, p=0.006) were independent predictors of survival in CRC. In the whole cohort, the enrolled patients were then divided into three groups according to their PT and APTT levels. The OS and DFS differed notably among the low-risk (PT<11.85 sec and APTT<25.85 sec), medium-risk (PT≥11.85 sec or APTT≥25.85 sec), and high-risk (PT≥11.85 sec and APTT≥25.85 sec) groups. Conclusion: Elevated levels of preoperative PT and APTT were predictors of poor outcomes in CRC patients. Moreover, the combination of preoperative PT and APTT can be a new prognostic stratification approach for more precise clinical staging of CRC.

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“…It is present during cellular proliferation of normal cells, premalignant and neoplastic cells but absent in cells that are in G0 phase [31]. MCM3, presented in a variety of human tumors, is involved in tumor proliferation [32], diagnosis [33], and prognosis. For example, Hua et al [34] reported that high mRNA expression levels of MCM2 and MCM3 were correlated with a poor outcome and thus might be clinically useful molecular prognostic markers in glioma.…”

Section: Discussionmentioning

confidence: 99%

Prognostic values and prospective pathway signaling of MicroRNA-182 in ovarian cancer: a study based on gene expression omnibus (GEO) and bioinformatics analysis

2019

J Ovarian Res

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BackgroundOvarian carcinoma (OC) is a common cause of death among women with gynecological cancer. MicroRNAs (miRNAs) are believed to have vital roles in tumorigenesis of OC. Although miRNAs are broadly recognized in OC, the role of has-miR-182-5p (miR-182) in OC is still not fully elucidated.MethodsWe evaluated the significance of miR-182 expression in OC by using analysis of a public dataset from the Gene Expression Omnibus (GEO) database and a literature review. Furthermore, we downloaded three mRNA datasets of OC and normal ovarian tissues (NOTs), GSE14407, GSE18520 and GSE36668, from GEO to identify differentially expressed genes (DEGs). Then the targeted genes of hsa-miR-182-5p (TG_miRNA-182-5p) were predicted using miRWALK3.0. Subsequently, we analyzed the gene overlaps integrated between DEGs in OC and predicted target genes of miR-182 by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. STRING and Cytoscape were used to construct a protein-protein interaction (PPI) network and the prognostic effects of the hub genes were analyzed.ResultsA common pattern of up-regulation for miR-182 in OC was found in our review of the literature. A total of 268 DEGs, both OC-related and miR-182-related, were identified, of which 133 genes were discovered from the PPI network. A number of DEGs were enriched in extracellular matrix organization, pathways in cancer, focal adhesion, and ECM-receptor interaction. Two hub genes, MCM3 and GINS2, were significantly associated with worse overall survival of patients with OC. Furthermore, we identified covert miR-182-related genes that might participate in OC by network analysis, such as DCN, AKT3, and TIMP2. The expressions of these genes were all down-regulated and negatively correlated with miR-182 in OC.ConclusionsOur study suggests that miR-182 is essential for the biological progression of OC.

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MCM3: A Novel Proliferation Marker in Oral Squamous Cell Carcinoma

Cited by 32 publications

References 35 publications

Minichromosome maintenance 3 promotes hepatocellular carcinoma radioresistance by activating the NF-κB pathway

Minichromosome maintenance 3 promotes hepatocellular carcinoma radioresistance by activating the NF-κB pathway

<p>Prediction of Poor Outcomes in Patients with Colorectal Cancer: Elevated Preoperative Prothrombin Time (PT) and Activated Partial Thromboplastin Time (APTT)</p>

Prognostic values and prospective pathway signaling of MicroRNA-182 in ovarian cancer: a study based on gene expression omnibus (GEO) and bioinformatics analysis

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