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ABSTRACT: Cystatin M is a secreted inhibitor of lysosomal cysteine proteases and increasing evidences indicate that it is a novel target for epigenetic silencing during mammary tumorigenesis. Aberrant promoter methylation is a well-known mechanism that participates in cystatin M silencing in breast cancer. However, the role of cystatin M in the gastric cancer remains to be elucidated. Immunohistochemistry was used to investigate the expression of cystatin M in 60 gastric carcinomas. Hypermethylation of cystatin M promoter was evaluated by the methylation-specific PCR (MSP) method in gastric carcinomas (tumor and paired adjacent non-tumor tissues). Reverse-transcriptase PCR and BSP were also performed on gastric cancer cell lines before and after treatment with 5-aza-2'-deoxycytidine (5-Aza-dC). Lost expression of cystatin M was observed in 42 of 60 (70%) gastric carcinomas. 55% (33 of 60) of primary tumors analyzed displayed cystatin M promoter hypermethylation, indicating that this aberrant characteristic is common in gastric malignancies. Moreover, a statistically significant inverse association was found between cystatin M methylation status and expression of the cystatin M protein in tumor tissues (p=0.027). We also found that patients with cystatin M promoter methylation had a significantly shorter survival time than those without this methylation (p=0.020). These results suggest that cystatin M promoter hypermethylation is one of the molecular mechanisms that accounts for reduced cystatin M gene expression in gastric carcinomas.
Biochemical and Biophysical Research Communications 12/2009; 391(1):1070-4. · 2.48 Impact Factor
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ABSTRACT: Colorectal cancer (CRC) is the third most common cancer in the world. Despite recent advances in diagnostics and treatment, prognosis for patients with advanced disease is still poor. microRNAs (miRNAs) are a class of endogenous, small noncoding RNA molecules which are crucial regulators of gene expression at the posttranscriptional level. miRNAs participate in many biological events and play an important role in various human diseases, including CRC.
This study is to identify the role of miR-141 in migration and invasion of CRC cells.
Expression of miR-141 and Smad interacting protein 1 (SIP1) were detected by real-time reverse-transcription polymerase chain reaction (RT-PCR) and Western blotting. The effect of miR-141 on migration and invasion of CRC cells was investigated using wound healing assay and Matrigel invasion assay in vitro. The regulation effect of miR-141 on SIP1 was evaluated by dual-luciferase reporter assay.
We demonstrated that miR-141 levels correlate inversely with SIP1 protein levels as well as cell migration and invasion of CRC cells. SIP1 was identified as a functional target of miR-141.
miR-141 regulates SIP1 to inhibit migration and invasion of CRC cells. miR-141 and SIP1 might be candidate therapeutic targets in CRC.
Digestive Diseases and Sciences 10/2009; 55(8):2365-72. · 2.12 Impact Factor
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ABSTRACT: Glioma is an extremely aggressive and lethal form of brain cancer. Despite recent advances in diagnostics and treatments, prognosis for advanced patients suffering from these diseases remains poor. Therefore, identification of new therapeutic targets for glioma is of significant importance. In this study, we identified the important role of Smad interacting protein 1 (SIP1; also known as ZEB2) in glioma. We firstly found that SIP1 expression was high in four tumorigenic glioma cell lines but low in two nontumorigenic glioma cell lines. By knockdown or overexpression assay, we discovered that knockdown of SIP1 expression statistically significantly inhibited cell migration and invasion of tumorigenic glioma cells, while overexpression of SIP1 promoted cell migration and invasion of nontumorigenic glioma cells. SIP1 knockdown inhibits and overexpression promotes glioma cell clonogenicity in vitro. Further studies identified that SIP1 overexpression inhibits expression of E-cadherin and enhances expression of mesenchymal proteins such as fibronectin and vimentin. This study supports the rationale for developing SIP1 as a potential therapeutic and diagnostic target for gliomas.
Journal of Neuro-Oncology 10/2009; 97(2):225-32. · 3.21 Impact Factor
