Therapeutic Targeting Of Microrna-31 In Lung Cancer
JOURNAL OF CLINICAL ONCOLOGY(2012)
摘要
e13567 Background: MicroRNAs (miRs) have emerged as powerful regulators of cellular processes and are frequently deregulated in cancer. Our previous work showed that miR-31 was overexpressed in human and murine lung cancers and repression of miR-31 inhibits lung cancer proliferation and tumorigenesis. Novel miR-31-targeting compounds were developed using a locked nucleic acid (LNA) drug platform. Compounds were tested in cell-based assays to assess levels of miR-31, miR-31-target genes and cell proliferation. A lead compound was chosen and we are currently examining its in vivo activity in human lung cancer cells and in murine transgenic lung tumor models. Methods: We previously developed a murine model of lung cancer by specifically overexpressing human cyclin E in the lung (CEO mice). The ED1 cell line was derived from a CEO mouse lung tumor. ED1 cells were transfected with the miR-31-LNA-targeting compounds and miR-31 levels and target genes quantified versus controls using RT-PCR assays. Cell prolifer...
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