Systematic analysis reveals tumor-enhancing and -suppressing microRNAs in Drosophila epithelial tumors

// Zhiqiang Shu 1, * , Yi-Chun Huang 1, * , William H. Palmer 1, 3 , Yoichiro Tamori 1, 4 , Gengqiang Xie 1 , Hui Wang 2 , Nan Liu 2 and Wu-Min Deng 1 1 Department of Biological Science, Florida State University, Tallahassee, Florida, USA 2 Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China 3 Current/Present address: Institute of Evolutionary Biology, University of Edinburgh, Edinburgh, UK 4 Current/Present address: Structural Biology Center, National Institute of Genetics and Department of Genetics, School of Life Science, SOKENDAI (The Graduate University for Advanced Studies), Mishima, Japan * These authors have contributed equally to this work Correspondence to: Wu-Min Deng, email: wumin@bio.fsu.edu Keywords : miRNA; RNA-Seq; lgl; nTSGs; tumorigenesis Received: August 25, 2017      Accepted: October 13, 2017      Published: November 01, 2017 ABSTRACT Despite their emergence as an important class of noncoding RNAs involved in cancer cell transformation, invasion, and migration, the precise role of microRNAs (miRNAs) in tumorigenesis remains elusive. To gain insights into how miRNAs contribute to primary tumor formation, we conducted an RNA sequencing (RNA-Seq) analysis of Drosophila wing disc epithelial tumors induced by knockdown of a neoplastic tumor-suppressor gene (nTSG) lethal giant larvae ( lgl ), combined with overexpression of an active form of oncogene Ras ( Ras V12 ), and identified 51 mature miRNAs that changed significantly in tumorous discs. Followed by in vivo tumor enhancer and suppressor screens in sensitized genetic backgrounds, we identified 10 tumor-enhancing (TE) miRNAs and 11 tumor-suppressing (TS) miRNAs that contributed to the nTSG defect-induced tumorigenesis. Among these, four TE and three TS miRNAs have human homologs. From this study, we also identified 29 miRNAs that individually had no obvious role in enhancing or alleviating tumorigenesis despite their changed expression levels in nTSG tumors. This systematic analysis, which includes both RNA-Seq and in vivo functional studies, helps to categorize miRNAs into different groups based on their expression profile and functional relevance in epithelial tumorigenesis, whereas the evolutionarily conserved TE and TS miRNAs provide potential therapeutic targets for epithelial tumor treatment.