miR-21 inhibitor sensitizes human OSCC cells to cisplatin.
ABSTRACT miR-21 as a tumor oncogenic molecule has been reported. However, whether miR-21 can affect the sensitivity of oral squamous cell carcinoma (OSCC) cells to cisplatin remain unclear. The aim of this study is to evaluate the roles of miR-21 in the sensitivity of OSCC cells to cisplatin. RT-PCR assay was performed to detect the expression of miR-21 in 10 pairs of OSCC and noncancerous tissue samples. Then As-miR-21 oligonucleotides were used to down the miR-21 expression. Finally, the effects of miR-21 downregulation the sensitivity of OSCC cells (CA-27) to cisplatin in vitro were also detected. The level of miR-21 expression in OSCC tissues was significantly higher than that in corresponding noncancerous tissues. Down the expression of miR-21 could significantly inhibit growth and induce apoptosis of CA-27 cells. Moreover, downregulation of miR-21 could sensitize CA-27 cells to cisplatin possibly by increasing cisplatin induced apoptosis. This study demonstrated that combination of cisplatin application with miR-21 downregulation might be a potential strategy for the treatment of human OSCC.
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ABSTRACT: Over the past several years it has become clear that alterations in the expression of microRNA (miRNA) genes contribute to the pathogenesis of most--if not all--human malignancies. These alterations can be caused by various mechanisms, including deletions, amplifications or mutations involving miRNA loci, epigenetic silencing or the dysregulation of transcription factors that target specific miRNAs. Because malignant cells show dependence on the dysregulated expression of miRNA genes, which in turn control or are controlled by the dysregulation of multiple protein-coding oncogenes or tumour suppressor genes, these small RNAs provide important opportunities for the development of future miRNA-based therapies.Nature Reviews Genetics 10/2009; 10(10):704-14. · 41.06 Impact Factor
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ABSTRACT: Due to the poor prognosis of pancreatic cancer, novel diagnostic modalities for early diagnosis and new therapeutic strategy are urgently needed. Recently, microRNA-21 (miR-21) was reported to be strongly overexpressed in pancreatic cancer as well as in other solid cancers. We investigated the functional roles of miR-21, which have not been fully elucidated in pancreatic cancer. miR-21 expression was assessed in pancreatic cancer cell lines (14 cancer cell lines, primary cultures of normal pancreatic epithelial cells and fibroblasts, and a human normal pancreatic ductal epithelial cell line) and pancreatic tissue samples (25 cancer tissues and 25 normal tissues) by quantitative real-time reverse transcription-PCR amplification. Moreover, we investigated the proliferation, invasion, and chemoresistance of pancreatic cancer cells transfected with miR-21 precursor or inhibitor. miR-21 was markedly overexpressed in pancreatic cancer cells compared with nonmalignant cells, and miR-21 in cancer tissues was much higher than in nonmalignant tissues. The cancer cells transfected with the miR-21 precursor showed significantly increased proliferation, Matrigel invasion, and chemoresistance for gemcitabine compared with the control cells. In contrast, inhibition of miR-21 decreased proliferation, Matrigel invasion, and chemoresistance for gemcitabine. Moreover, miR-21 positively correlated with the mRNA expression of invasion-related genes, matrix metalloproteinase-2 and -9, and vascular endothelial growth factor. These data suggest that miR-21 expression is increased in pancreatic cancer cells and that miR-21 contributes to the cell proliferation, invasion, and chemoresistance of pancreatic cancer.Molecular Cancer Therapeutics 06/2009; 8(5):1067-74. · 5.60 Impact Factor
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ABSTRACT: Five years into the 'small RNA revolution' it is hard not to share in the excitement about the rapidly unravelling biology of microRNAs. Since the discovery of the first microRNA gene, lin-4, in the nematode Caenorhabditis elegans, many more of these short regulatory RNA genes have been identified in flowering plants, worms, flies, fish, frogs and mammals. Currently, about 2% of the known human genes encode microRNAs. MicroRNAs are essential for development and this review will summarise our current knowledge of animal microRNA function. We will also discuss the emerging links of microRNA biology to stem cell research and human disease, in particular cancer.Development 12/2005; 132(21):4653-62. · 6.21 Impact Factor