• Asian Pacific Journal of Cancer Prevention
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• v.17 no.5
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• pp.2383-2388
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• 2016

Background: The reversion-inducing-cysteine-rich protein with Kazal motifs (RECK) gene is a novel transformation suppressor gene linked to several malignancies. Objective: To analyze any association between RECK gene rs10814325 single-nucleotide polymorphism (SNP) and HCC susceptibility with various clinicopathological and laboratory data. Materials and Methods: RECK gene rs10814325 SNP was estimated, using real-time PCR, in 30 HCC patients on top of HCV infection, 30 HCV related cirrhotic patients and 30 healthy controls. Results: No special pattern of association could be detected on comparing the RECK gene rs10814325 genotypes(P=0.5), or alleles(P=0.49) among the studied groups. HCC patients with TT genotype had younger age (mean of $54.1{\pm}6.0$ years vs $60.6{\pm}10.2$ years for TC/CC genotypes, P=0.035). Abdominal distension was significantly greater in TT genotype patients (75% vs 30%for TC/CC genotypes, P=0.045). The TT genotype was present in 75% of patients with lymph node metastasis. Serum GGT levels were higher in TT genotype patients [80 (48.5-134.8) IU/L vs 40 (33-87.5) IU/L for TC/CCgenotypes], and lower limb edema was observed in 60% for TT vs 20% for TC/CCgenotypes, but both just failed to reach significance (p=0.05 and p=0.06 respectively). Conclusions: RECK gene rs10814325 T>C could not be considered a risk factor for HCC development on top of HCV, but may be related to the disease progression and metastasis.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.3
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• pp.2113-2118
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• 2013

Aim and Background: Cervical cancer remains the third most common cancer in women globally after breast and colorectal cancer. Well-characterized biomarkers are necessary for early diagnosis and to predict metastatic progression and effective therapy. MiRNAs can regulate gene expression, cell growth, differentiation and apoptosis by targeting mRNAs for translational repression or degradation in tumor cells. The present study was conducted to assess expression of miR93, miR200a, RECK, MMP2, MMP9 in invasive cervical carcinoma, and analyze their clinical significance. Method: A total of 116 patients with invasive cervical carcinoma and 100 patients undergoing hysterectomy for benign lesions were retrospectively examined. Quantitative real-time PCR was performed to determine expression of miR93 and miR200a while RECK, MMP2, MMP9 and MVD were assessed by immunohistochemical staining. Results: Cervical carcinoma patients demonstrated up-regulation of miR-93, miR-200a, MMP2 and MMP9, with down-regulation of RECK as compared to benign lesion tissues. RECK was significantly inversely related to invasion and lymphatic metastasis. The 5-year survival rate for patients with strong RECK expression was significantly higher than that with weakly expressing tumors. Conclusion: MiR-93 and miR-200a are associated with metastasis and invasion of cervical carcinoma. Thus together with RECK they are potential prognostic markers for cervical carcinoma. RECK cooperating with MMP2, MMP9 expression is a significant prognostic factor correlated with long-term survival for patients with invasive cervical carcinoma.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.2
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• pp.829-834
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• 2013

Background: MicroRNAs are noncoding RNA molecules that posttranscriptionally regulate gene expression. The aim of this study was to determine the role of microRNA-21 in cholangiocarcinomas and its relationship to cholangiocarcinoma RBE cell capacity for invasion and metastasis. Methods: MicroRNA-21 expression was investigated in 41 cases of cholangiocarcinoma samples by in situ hybridization and real-time PCR. Influence on cholangiocarcinoma cell line invasion and metastasis was analyzed with microRNA-21 transfected cells. In addition, regulation of reversion-inducing-cysteine-rich protein with kazal motifs (RECK) by microRNA-21 was elucidated to identify mechanisms. Results: In situ hybridization and real-time quantitative PCR results for patients with lymph node metastasis or perineural invasion showed significantly high expression of microRNA-21 (P<0.05). There was a dramatic decrease in cholangiocarcinoma cell line invasion and metastasis ability after microRNA-21 knockdown (P<0.05). However, overexpression significantly increased invasion and metastasis (P<0.05). Real-time PCR and Western-blot analysis showed that microRNA-21 could potentially inhibit RECK expression in RBE cells. Survival analysis showed that patients with higher expression levels of microRNA-21 more often had a poor prognosis (P<0.05). Conclusions: MicroRNA-21 may play an important role in cholangiocarcinoma invasion and metastasis, suggesting that MicroRNA-21 should be further evaluated as a biomarker for predicting cholangiocarcinoma prognosis.

• BMB Reports
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• v.36 no.1
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• pp.128-137
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• 2003

Matrix metalloproteinases (MMPs), zinc dependent proteolytic enzymes, cleave extracellular matrix (ECM: collagen, laminin, firbronectin, etc) as well as non-matrix substrates (growth factors, cell surface receptors, etc). The deregulation of MMPs is involved in many diseases, such as tumor metastasis, rheumatoid arthritis, and periodontal disease. Metastasis is the major cause of death among cancer patients. In this review, we will focus on the roles of MMPs in tumor metastasis. The process of metastasis involves a cascade of linked, sequential steps that involve multiple host-tumor interactions. Specifically, MMPs are involved in many steps of tumor metastasis. These include tumor invasion, migration, host immune escape, extravasation, angiogenesis, and tumor growth. Therefore, without MMPs, the tumor cell cannot perform successful metastasis. The activities of MMPs are tightly regulated at the gene transcription levels, zymogen activation by proteolysis, and inhibition of active forms by endogenous inhibitors, tissue inhibitor of metalloproteinase (TIMP), and RECK. The detailed regulations of MMPs are described in this review.