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Matrix metalloproteinase-7 may serve as a novel biomarker for cervical cancer.

ABSTRACT: The biological and clinical significance of matrix metalloproteinase-7 (MMP-7) in cervical cancer remains unknown. Here, we investigated the function of MMP-7 in cervical cancer cells and evaluated its clinical significance in both tissues and serum from cervical cancer patients.First, we analyzed the expression of MMP-7 in cervical cancer using Oncomine microarray data and examined its expression in cervical tissues by quantitative real-time polymerase chain reaction and Western blotting. Second, we utilized gene silencing to explore the role of MMP-7 in cells. Finally, we examined the MMP-7 levels in patients with cervical cancer and normal serum by enzyme-linked immunosorbent assay. Moreover, we further investigated the relationship between MMP-7 expression and pathological features.The mRNA and protein MMP-7 levels were higher in cervical cancer tissues than in healthy controls. Silencing of MMP-7 significantly decreased cervical cancer cell proliferation, migration, and invasion. The serum MMP-7 levels were significantly higher in cervical cancer patients than in healthy subjects (P<0.01). Further, higher MMP-7 expression was associated with increased lymph metastasis (P=0.021), pathological grade (P=0.039, P=0.047), and clinical stage (P=0.049, P=0.046).MMP-7 appears to act as an oncogene in cervical cancer cells and is involved in cell proliferation, migration, and invasion. MMP-7 expression was significantly higher in the tissue and serum of cervical cancer patients compared to healthy individuals and was correlated with increased pathalogical grade, clinical stage, and lymph metastasis. Therefore, our data provide novel evidence that MMP-7 may be a clinically relevant biomarker for cervical cancer.

SUBMITTER: Zhu L

PROVIDER: S-EPMC6055895 | biostudies-other | 2018

REPOSITORIES: biostudies-other

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Matrix metalloproteinase-7 may serve as a novel biomarker for cervical cancer.

Zhu Linyan L Zheng Xiaojiao X Du Yongming Y Xing Yan Y Xu Kejun K Cui Lining L

OncoTargets and therapy 20180720

<h4>Background</h4>The biological and clinical significance of matrix metalloproteinase-7 (MMP-7) in cervical cancer remains unknown. Here, we investigated the function of MMP-7 in cervical cancer cells and evaluated its clinical significance in both tissues and serum from cervical cancer patients.<h4>Methods</h4>First, we analyzed the expression of MMP-7 in cervical cancer using Oncomine microarray data and examined its expression in cervical tissues by quantitative real-time polymerase chain r ...[more]

PMID: 30050312

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Project description:Matrix metalloproteinases (MMPs) play an essential role in various physiological events. Recent studies have revealed its carcinogenic effect in malignancies. However, the different expression patterns, prognostic value, and immunological value of MMPs in pancreatic ductal adenocarcinoma (PDAC) are yet to be comprehensively explored. We utilized Gene Expression Profiling Interactive Analysis (GEPIA) and Gene Expression Omnibus databases to explore the abnormal expression of MMPs in PDAC. Then, Kaplan-Meier survival curve and Cox regression analysis were performed to assess the prognostic value of MMPs. Association between MMPs expression and clinicopathological features was analyzed through UALCAN website. Functional annotations and GSEA analysis were performed to excavate the possible signaling pathways involving prognostic-related MMP. TIMER and TISCH database were used to performed immune infiltration analysis. The expression of prognostic-related MMP in pancreatic cancer cell lines and normal pancreatic cells was detected by Real time quantitative PCR. We observed that 10 MMP genes were consistently up-regulated in GEPIA and GSE62452 dataset. Among them, five highly expressed MMPs (MMP1, MMP3, MMP11, MMP14, MMP28) were closely related to poor clinical outcomes of PDAC patients. Cox regression analysis indicated MMP28 was a risk factor influencing the overall survival of patients. In the clinicopathological analysis, up-regulated MMP28 was significantly associated with higher tumor grade and the mutation status of TP53. GSEA analysis demonstrated that high expression of MMP28 was involved in "interferon_alpha_response" and "P53_pathway". Immune infiltration analysis showed that there was no correlation between MMP28 expression and immune cell infiltration. Single-cell sequencing analysis showed MMP28 has strong correlations with malignant cells and stromal cells infiltration in the tumor microenvironment. And MMP28 was highly expressed in various pancreatic cancer cell lines. In conclusion, MMP28 may represent a potential prognosis biomarker and novel therapeutic molecular targets for PDAC.

Project description:We recently developed novel matrix metalloproteinase-2 (MMP-2) inhibitor small molecules for cardioprotection against ischemia/reperfusion injury and validated their efficacy in ischemia/reperfusion injury in cardiac myocytes. The aim of the present study was to test our lead compounds for cardioprotection in vivo in a rat model of acute myocardial infarction (AMI) in the presence or absence of hypercholesterolemia, one of the major comorbidities affecting cardioprotection. Normocholesterolemic adult male Wistar rats were subjected to 30 min of coronary occlusion followed by 120 min of reperfusion to induce AMI. MMP inhibitors (MMPI)-1154 and -1260 at 0.3, 1, and 3 µmol/kg, MMPI-1248 at 1, 3, and 10 µmol/kg were administered at the 25th min of ischemia intravenously. In separate groups, hypercholesterolemia was induced by a 12-week diet (2% cholesterol, 0.25% cholic acid), then the rats were subjected to the same AMI protocol and single doses of the MMPIs that showed the most efficacy in normocholesterolemic animals were tested in the hypercholesterolemic animals. Infarct size/area at risk was assessed at the end of reperfusion in all groups by standard Evans blue and 2,3,5-triphenyltetrazolium chloride (TTC) staining, and myocardial microvascular obstruction (MVO) was determined by thioflavine-S staining. MMPI-1154 at 1 µmol/kg, MMPI-1260 at 3 µmol/kg and ischemic preconditioning (IPC) as the positive control reduced infarct size significantly; however, this effect was not seen in hypercholesterolemic animals. MVO in hypercholesterolemic animals decreased by IPC only. This is the first demonstration that MMPI-1154 and MMPI-1260 showed a dose-dependent infarct size reduction in an in vivo rat AMI model; however, single doses that showed the most efficacy in normocholesterolemic animals were abolished by hypercholesterolemia. The further development of these promising cardioprotective MMPIs should be continued with different dose ranges in the study of hypercholesterolemia and other comorbidities.

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Matrix metalloproteinase-7 may serve as a novel biomarker for cervical cancer.

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Matrix metalloproteinase-7 may serve as a novel biomarker for cervical cancer.

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