title: Bioinformatic Studies to Predict MicroRNAs with the Potential of Uncoupling RECK Expression from Epithelial-Mesenchymal Transition in Cancer Cells.
abstract: RECK is downregulated in many tumors, and forced RECK expression in tumor cells often results in suppression of malignant phenotypes. Recent findings suggest that RECK is upregulated after epithelial-mesenchymal transition (EMT) in normal epithelium-derived cells but not in cancer cells. Since several microRNAs (miRs) are known to target RECK mRNA, we hypothesized that certain miR(s) may be involved in this suppression of RECK upregulation after EMT in cancer cells. To test this hypothesis, we used three approaches: (1) text mining to find miRs relevant to EMT in cancer cells, (2) predicting miR targets using four algorithms, and (3) comparing miR-seq data and RECK mRNA data using a novel non-parametric method. These approaches identified the miR-183-96-182 cluster as a strong candidate. We also looked for transcription factors and signaling molecules that may promote cancer EMT, miR-183-96-182 upregulation, and RECK downregulation. Here we describe our methods, findings, and a testable hypothesis on how RECK expression could be regulated in cancer cells after EMT.
authors.affiliation: Laboratory for Malignancy Control Research, Medical Innovation Center, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Gynecology and Obstetrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Ryusuke
authors.initials: R
authors.lastname: Murakami
authors.affiliation: Laboratory for Malignancy Control Research, Medical Innovation Center, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Kanako
authors.initials: K
authors.lastname: Yuki
authors.affiliation: Laboratory for Malignancy Control Research, Medical Innovation Center, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Yoshida
authors.affiliation: Laboratory for Malignancy Control Research, Medical Innovation Center, Graduate School of Medicine, Kyoto University, Kyoto, Japan.; Department of Molecular Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Noda
keywords: EMT; RECK; SOX2; TEAD4; cancer; miR-183-96-182; paired data correlation