Purpose: microRNAs (miRNA) are small RNAs that function as post-transcriptional regulators of gene expression. Recent evidence has shown that some miRNAs can act as oncogenes or tumor suppressors. This study was conducted to evaluate the potential association of miRNA expression with clinical outcome in patients with gastric cancer. Experimental Design: Expression of 250 human mature miRNAs was measured by real-time PCR on paraffin-embedded tumor samples of 21 patients with gastric cancer stage III uniformly treated with surgical resection followed by chemoradiation. We identified the miRNAs correlated with disease-free and overall survival times, and the results were evaluated including 24 other patients. In vitro cell proliferation and radiosensitivity studies were done to support clinical data. Results:The results revealed that down-regulation of miR-451was associated with worse prognosis. miR-451 was detected by in situ hybridization in epithelial cells and showed decreased expression in gastric and colorectal cancer versus nontumoral tissues. Overexpression of miR-451in gastric and colorectal cancer cells reduced cell proliferation and increased sensitivity to radiotherapy. Microarray and bioinformatic analysis identified the novel oncogene macrophage migration inhibitory factor (MIF) as a potential target of miR-451. In fact, overexpression of miR451down-regulated mRNA and protein levels of MIF and decreased expression of reporter genes with MIF target sequences. Moreover, we found a significant inverse correlation between miR451and MIF expression in tumoral gastric biopsies. Conclusions: These findings support the role of miR-451as a regulator of cancer proliferation and opennew perspectives for the development of effective therapies for chemoradioresistant cancers.
Severe discordance is more frequent and has greater morbidity in monochorionic than dichorionic twins. The most frequent findings in the placentas of severely discordant twins were small placental weight and umbilical cord abnormalities.
Cases of preterm PROM may be classified according to placental histologic findings, and these groups have different clinical manifestations, prognoses, and outcomes.
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