MMP-9-1562 C/T single nucleotide polymorphism associates with increased MMP-9 level and activity during papillary thyroid carcinoma progression

Rončević, Jelena; Djoric, Ilona; Šelemetjev, Sonja; Janković, Jelena; Dencic, Tijana; Bozic, Vesna; Cvejić, Dubravka

doi:10.1016/j.pathol.2018.10.008

Cited by 19 publications

(22 citation statements)

References 36 publications

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“…ABL1 is a protooncogene that encodes a protein tyrosine kinase involved in a variety of cellular processes, including cell division, adhesion, differentiation, and response to stress [ 30 ]. Proteins of the matrix metalloproteinase (MMP) family are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis [ 31 ]. AKT serine/threonine kinase 2 (AKT2) is a putative oncogene encoding a protein belonging to a subfamily of serine/threonine kinases containing SH2-like (Src homology 2-like) domains.…”

Section: Discussionmentioning

confidence: 99%

Aberrant methylation and microRNA-target regulation are associated with downregulated NEURL1B: a diagnostic and prognostic target in colon cancer

Liu

Zhang

et al. 2020

Cancer Cell Int

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Background Aberrant methylation and miRNA-target-gene regulation function as important mechanisms for gene inactivation in colon carcinogenesis. Although a serious of molecular events (such as aberrant alterations of genomics and epigenetics) have been identified to be related to prognostic in colon cancer (CC) patients, beneficial biomarkers for early diagnosis and prognostic evaluation remain largely unknown. Methods In our study, the role of NEURL1B, including gene expression analysis, methylation characteristic, miRNA-target regulation, diagnostic and prognostic significance, were evaculated using multiple bioinformatic tools based on TCGA database and clinical samples. Results Our data showed that NEURL1B was aberrantly downregulated in CC, regardless of the mRNA level or protein level. Moreover, ROC curve and multivariate Cox regression analysis demonstrated that NEURL1B was a diagnostic and independent prognostic facter for CC patients. Of interest, methylation of NEURL1B was also high and closely associated with poor survival in CC. In addition, multiple NEURL1B-target miRNAs were found to be overexpressed in CC tissues. Thus, our findings suggested that NEURL1B participated in the pathological processes of CC as a tumor suppressor gene. Double management, including DNA methylation modification and miRNA-target regulation, were considered to be related to the downregulation of NEURL1B. Importantly, there existing be an significant intersection between miRNAs-target pathways and NEURL1B-target pathways, suggesting that miR-17 and miR-27a might promote tumor cell malignant property by targeting NEURL1B degradation via the activation of PI3K/AKT signaling pathway. Conclusions Taking together, the first investigation of NEURL1B in CC provide us a strong evidences that it might be served as a potential biomarkers for early diagnosis and prognostic evaluation in CC.

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Section: Discussionmentioning

confidence: 99%

Aberrant methylation and microRNA-target regulation are associated with downregulated NEURL1B: a diagnostic and prognostic target in colon cancer

Liu

Zhang

et al. 2020

Cancer Cell Int

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“…In particular, interleukin-1 has dual roles of anti-tumor and pro-tumor [43]. Positive regulation of MAP kinase activity and metalloendopeptidase activity are thought to be associated with thyroid cancer [44,45]. This is a validation of the major carcinogenic event of PTC is the activation of MAPK.…”

Section: Discussionmentioning

confidence: 99%

Identification of hub genes in papillary thyroid carcinoma: robust rank aggregation and weighted gene co-expression network analysis

et al. 2020

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Background: Papillary thyroid carcinoma (PTC), which is the most common endocrine malignancy, has been steadily increasing worldwide in incidence over the years, while mechanisms underlying the pathogenesis and diagnostic for PTC are incomplete. The purpose of this study is to identify potential biomarkers for diagnosis of PTC, and provide new insights into pathogenesis of PTC.Methods: Based on weighted gene co-expression network analysis, Robust Rank Aggregation, functional annotation, GSEA and DNA methylation, were employed for investigating potential biomarkers for diagnosis of PTC.Results: Black and turquoise modules were identified in the gene co-expression network constructed by 1807 DEGs that from 6 eligible gene expression profiles of Gene Expression Omnibus database based on Robust Rank Aggregation and weighted gene co-expression network analysis. Hub genes were significantly down-regulated and the expression levels of the hub genes were different in different stages in hub gene verification. ROC curves indicated all hub genes had good diagnostic value for PTC (except for ABCA6 AUC = 89.5%, the 15 genes with AUC > 90%). Methylation analysis showed that hub gene verification ABCA6, ACACB, RMDN1 and TFPI were identified as differentially methylated genes, and the decreased expression level of these genes may relate to abnormal DNA methylation. Moreover, the expression levels of 8 top hub genes were correlated with tumor purity and tumor-infiltrating immune cells. These findings, including functional annotations and GSEA provide new insights into pathogenesis of PTC. Conclusions:The hub genes and methylation of hub genes may as potential biomarkers provide new insights for diagnosis of PTC, and all these findings may be the direction to study the mechanisms underlying of PTC in the future.

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“…In the process of degradation, large amounts of vascular endothelial growth factors stored in the extracellular matrix can be released to induce tumor angiogenesis and provide the necessary nutritional basis and pathway for tumor cell invasion [25]. MMP-9, also known as Gelatinase B, can degrade and destroy extracellular matrix and basement membrane near the surface of tumor cells, release a large number of growth promoting factors, and make tumor cells invade the surrounding tissues along the missing basement membrane, promoting the invasion and metastasis of tumor cells [26][27][28].…”

Section: Discussionmentioning

confidence: 99%

RUNX3 Inhibits the Invasion and Metastasis of Human Colon Cancer HT‐29 Cells by Upregulating MMP‐2/9

Xue

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Objective. To investigate the effect of Runt-associated transcription factor 3 (RUNX3) on the invasion and metastasis of human colon cancer HT-29 cells and to preliminarily explore the mechanism of its anticancer effect. Methods. e RUNX3 plasmid vector was transfected into human colon cancer HT-29 cells by liposome-mediated transfection, while the empty vector and the blank group were used as the control group. After Geneticin (G418) screening, HT-29 cells with stable expression of RUNX3 gene were obtained. e expressions of mRNA and proteins of RUNX3 and metalloproteinases (MMP)-2/9 were detected by reverse transcription-polymerase chain reaction (RT-PCR) and western blot. Cell proliferation was determined by MTT assay. e effect of RUNX3 on invasion and metastasis of HT-29 cells was evaluated by scratch injury assay, Transwell chamber, and Matrigel invasion model. Results. RUNX3 was expressed stably in HT-29 cells after transfection. e expressions of RUNX3 mRNA and proteins in the experimental group were significantly higher than those in the blank/empty vector groups. Meanwhile, the expressions of MMP-2/9 mRNA and proteins in the observation group were significantly lower than those in the blank group and the empty vector group. e proliferation and migration ability in the experimental group was significantly lower than blank/ empty vector groups from the third day. Transwell chamber experiment and Matrigel invasion assay showed that the number of Transwell cells was decreased significantly than blank/empty vector groups, but no difference was found between the blank group and the empty vector group. Conclusion. RUNX3 can inhibit the invasion and metastasis of human colon cancer HT-29 cells, and the mechanism may be related to decreased expression of MMP-2 and MMP-9.

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MMP-9-1562 C/T single nucleotide polymorphism associates with increased MMP-9 level and activity during papillary thyroid carcinoma progression

Cited by 19 publications

References 36 publications

Aberrant methylation and microRNA-target regulation are associated with downregulated NEURL1B: a diagnostic and prognostic target in colon cancer

Aberrant methylation and microRNA-target regulation are associated with downregulated NEURL1B: a diagnostic and prognostic target in colon cancer

Identification of hub genes in papillary thyroid carcinoma: robust rank aggregation and weighted gene co-expression network analysis

RUNX3 Inhibits the Invasion and Metastasis of Human Colon Cancer HT‐29 Cells by Upregulating MMP‐2/9

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