Epigenetic and oncogenic regulation of SLC16A7 (MCT2) results in protein over-expression, impacting on signalling and cellular phenotypes in prostate cancer.

摘要: // Nelma Pertega-Gomes 1 , Jose R. Vizcaino 2 Sergio Felisbino 3 Anne Y. Warren 4 Greg Shaw Jonathan Kay 1,5 Hayley Whitaker Andy G. Lynch 6 Lee Fryer 1,* David E. Neal 1,7,* and Charles Massie Uro-oncology Research Group, CRUK Cambridge Institute, Cambridge, UK Department of Pathology, Centro Hospitalar do Porto, Portugal Morphology, Institute Biosciences, Sao Paulo State University (UNESP), Paulo, Brazil Histopathology, Hospitals NHS Foundation Trust, Cambridge, UK 5 Molecular Diagnostics Therapeutics College London, London, UK Statistics Computational Biology 7 Urology, Oncology, Addenbrooke’s Hospital, * These authors have contributed equally to this work Correspondence to: Pertega-Gomes, email: Keywords : monocarboxylate transporter 2, prostate cancer, castrate resistant disease, malignant phenotype Received February 10, 2015 Accepted April 30, Published June 02, Abstract Monocarboxylate Transporter (MCT2) is a major pyruvate encoded by the SLC16A7 gene. Recent studies pointed consistent overexpression MCT2 in cancer (PCa) suggesting as putative biomarker molecular target. Despite importance observation mechanisms involved regulation are unknown. Through an integrative analysis we discovered that selective demethylation internal SLC16A7/MCT2 promoter recurrent event independent PCa cohorts. This associated with expression isoforms differing only 5’-UTR translational control motifs, providing one contributing mechanism for protein PCa. Genes co-expressed also clustered oncogenic-related pathways effectors these signalling were found bind at gene locus. Finally, knock-down attenuated growth cells. The present study unveils unexpected epigenetic identifies link between SLC16A7/MCT2, Androgen Receptor (AR), ETS-related (ERG) other oncogenic results underscore combining data from epigenetic, transcriptomic level changes allow more comprehensive insights into underlying expression, our case provide additional weight candidate target