| Tumors located at the oesophagus, paunch, small intestine, large intestine, liver,gallbladder and pancreas, where are the sites for food transportation, digestion orabsorption, are called digestive system tumors. At present, digestive system tumorsare the most common tumors wordwide, whose global incidence and death rate areabout30%, its incelence can reach about50%of total tumors in China.Esophageal cancer is sixth leading cause of cancer death worldwide with avariable geographic distribution. Two major histological types have been identified,esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC),regarding to different etiologic and pathologic characteristics. EAC is common inwestern countries while ESCC is frequent in east Asia, especially in China whoseincidence in the high-risk northern and central China exceeds100cases per100000people per year. Despite improvements in the diagnosis and treatment of this cancer,the overall survival for advanced and metastatic esophageal cancer is still poor, with a5-year survival rate of less than20%after surgery in China. Thus, there is a great needto disclose molecular mechanisms of pathogenesis of esophageal cancer to identifymore tumor specific biomarkers and therapeutic targets for early diagnosis andtreatment.MiRNAs are an endogenous class of20-25nucleotide-long single-strandednoncoding RNAs that regulate gene expression at the posttranscriptional level bybinding to the3’-untranslated region (3’-UTR) of mRNA which subsequently leads tomRNA degradation and translation repression. Previous studies have demonstratedthat a single miRNA may target multiple genes due to the imperfect complementaritywith target mRNA, while the expression of a single gene may be modulated bydifferent miRNAs. The remarkable performance of individual miRNAs to modulatemultiple transcripts allows miRNAs to control a variety of physiological processessuch as cell proliferation, differentiation and apoptosis. Thus, alterations in miRNAexpression are thought to play critical roles in cancer initiation and progressionthrough regulating the expression of various oncogenes and tumor suppressive genes.MicroRNA (miRNA), acting as tumour suppressor gene and oncogene, has aclose connection with the progress and development of various cancers. However, theinvolvement of miRNA in esophageal carcinogenesis is still not fully elucidated. Inthis study, we showed that over-expression of miR-203in esophageal cancer cellsinhibited cell proliferation and promoted cell apoptosis. Further observationsdemonstrated that miR-203suppressed cell migration and invasion, down-regulated miR-21expression and impeded the anchorage-independent growth in vitro andxenograft growth in vivo of esophageal cancer cells, indicating that miR-203playstumor suppressor roles in esophageal cancer. To understand molecular mechanism fortumor-suppressive roles of miR-203described above, we identified small GTPase Ranas a promising downstream target of miR-203confirmed by luciferase assay. Theexpression of Ran was significantly decreased in miR-203-transfected Ec-109cellsand restoration of Ran expression in these cells could in turn partially rescue theanti-tumor effects of miR-203and increase miR-21expression, suggesting that Ranplays critical roles in miR-203-mediated tumor suppression and miR-21down-regulation. In conclusion, our findings suggested that the alteration of miR-203may be one of the critical events that lead to the deregulation in the expression ofoncogenic protein small GTPase Ran and oncomir miR-21in esophageal cancer. Ourresults revealed a great potential for miR-203in esophageal cancer treatment.To investigate the implication of P27expression and DNA ploidy in the clinicalpathological features of colon cancinoma, the expressions of P27and the DNAcontent were investigated by immnunohistochemistry and flow cytometry in130cases, respectively. The relationships of P27expression and DNA ploidy with celldifferentiation, invasions, lymph node metastases, TNM classfication of coloncancinoma were analyzed. Data showed that the expressions of P27was lower andDNA content was higher in colon cancer tissues compared to peritumoral tissues(P<0.05). P27expression is assocated with Ducks stages and tumor malignancy(P<0.05). Our data suggested that p27expression and DNA Ploidy can serve asbiomarkers for clinical staging and prognosis of colon cancer. |
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