Previous gene expression studies have shown that these cell lines

Previous gene expression studies have shown that these cell lines resemble the primary tumor cells and can be grouped as basal or luminal like breast cancer subtypes. These cell lines inhibitor are highly variable in their migration and invasion capability BT474, MDA MB 468, T47D, ZR 75 1, MCF7, SK BR3 represent less invasive breast cancer cell lines, while MDA MB 231, HS578T, BT549, SUM159 are more invasive. MCF10A and MCF12A are two immortalized breast epithelial cell lines that are non tumorigenic, but were classified as basal like cell lines based on gene expression profiles. Using highly stringent criteria, we identified a group of 11 miRNAs that were most differentially expressed between the invasive and less invasive cell lines, including several miRNAs that have been linked to breast cancer previously, such as miR 200c, miR 203, miR 205, miR Inhibitors,Modulators,Libraries 375, miR 141, and miR 146a.

Introduction of exogen ous miR 200c, miR 205, and miR 375 mimics in the inva sive breast Inhibitors,Modulators,Libraries cancer cell line MDA MB 231 inhibited cell migration and invasion suggesting that these miRNAs may play important roles Inhibitors,Modulators,Libraries in maintaining the invasiveness of this cell line. Using gene expression array analysis, we also identified candidate genes affected by the exogenous miRNA mimics in MDA MB 231 cells. IPA analysis revealed that genes affected by miR 200c, miR 205, and miR 375 are involved in cellular movement and cell to cell signaling. Most significantly, our integrated analysis suggested that miR 200c might play a pivotal role in regulating cell mi gration and invasion, as 27 of the 35 differentially expressed genes were miR 200c targets.

Inhibitors,Modulators,Libraries This is consist ent with the migration and invasion experimental results showing that the miR 200c mimic is more potent than miR 205 and miR 375 mimics in inhibiting the mi gration and invasion of MDA MB 231 cells. CDH1 was found to be at the core of the molecu lar Inhibitors,Modulators,Libraries network regulated by miR 200c. CDH1 acts as a hub connected by several neighborhood genes that play im portant roles in cell migration and invasion. To further understand the function of the three miRNAs, it was necessary to identify their true targets in breast selleckchem Crizotinib cancer cells. The computational prediction of miRNA targets still faces significant challenges. The most widely used tools are characterized by a significant proportion of false positive interactions because post transcriptional regulation is context dependent. On the basis of increas ing experimental evidence supporting the hypothesis that miRNAs can act through target degradation, it has been proposed that target predictions could be integrated with miRNA and gene expression profiles to select functional miRNA mRNA relationships.

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