Malignant Germ Cell Tumors Display Common MicroRNA Profiles Resulting in Global Changes in Expression of Messenger RNA Targets

作者：Roger D. Palmer, Matthew Jonathan Murray, Harpreet Kaur Saini, Stijn van Dongen, Cei Abreu‐Goodger, Balaji Muralidhar, Mark R. Pett, Claire M. Thornton, James Christopher Nicholson, Anton James Enright, Nicholas Coleman, on behalf of the Children's Cancer and Leukaemia Group · 发表于：Cancer Research · 年份：2010 · DOI：10.1158/0008-5472.can-09-3301 · 被引用次数：294 · 研究领域：Testicular diseases and treatments、Cancer-related molecular mechanisms research、MicroRNA in disease regulation

Despite their extensive clinical and pathologic heterogeneity, all malignant germ cell tumors (GCT) are thought to originate from primordial germ cells. However, no common biological abnormalities have been identified to date. We profiled 615 microRNAs (miRNA) in pediatric malignant GCTs, controls, and GCT cell lines (48 samples in total) and re-analyzed available miRNA expression data in adult gonadal malignant GCTs. We applied the bioinformatic algorithm Sylamer to identify miRNAs that are of biological importance by inducing global shifts in mRNA levels. The most significant differentially expressed miRNAs in malignant GCTs were all from the miR-371-373 and miR-302 clusters (adjusted P < 0.00005), which were overexpressed regardless of histologic subtype [yolk sac tumor (YST)/seminoma/embryonal carcinoma (EC)], site (gonadal/extragonadal), or patient age (pediatric/adult). Sylamer revealed that the hexamer GCACTT, complementary to the 2- to 7-nucleotide miRNA seed AAGUGC shared by six members of the miR-371-373 and miR-302 clusters, was the only sequence significantly enriched in the 3'-untranslated region of mRNAs downregulated in pediatric malignant GCTs (as a group), YSTs and ECs, and in adult YSTs (all versus nonmalignant tissue controls; P < 0.05). For the pediatric samples, downregulated genes containing the 3'-untranslated region GCACTT showed significant overrepresentation of Gene Ontology terms related to cancer-associated processes, whereas for downregulated gene...