Oncotarget

Research Papers:

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

Zhiqiang Shu, Yi-Chun Huang, William H. Palmer, Yoichiro Tamori, Gengqiang Xie, Hui Wang, Nan Liu, Wu-Min Deng _

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Oncotarget. 2017; 8:108825-108839. https://doi.org/10.18632/oncotarget.22226

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Abstract

Zhiqiang Shu1,*, Yi-Chun Huang1,*, William H. Palmer1,3, Yoichiro Tamori1,4, Gengqiang Xie1, Hui Wang2, Nan Liu2 and Wu-Min Deng1

1Department of Biological Science, Florida State University, Tallahassee, Florida, USA

2Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China

3Current/Present address: Institute of Evolutionary Biology, University of Edinburgh, Edinburgh, UK

4Current/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 (RasV12), 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.


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