Systematic analysis reveals tumor-enhancing and -suppressing microRNAs in Drosophila epithelial tumors.
Systematic analysis reveals tumor-enhancing and -suppressing microRNAs in Drosophila epithelial tumors.
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DOI：
10.18632/oncotarget.22226
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发表时间：
2017-12-12
期刊：
影响因子：
--
通讯作者：
Deng WM
中科院分区：
文献类型：
--
作者：
Shu Z;Huang YC;Palmer WH;Tamori Y;Xie G;Wang H;Liu N;Deng WM
尽管它们作为一类重要的非编码RNA参与癌细胞的转化、侵袭和迁移，但microRNAs(MiRNAs)在肿瘤发生中的确切作用仍然不清楚。为了深入了解miRNAs在原发肿瘤形成中的作用，我们对果蝇翼盘上皮肿瘤进行了RNA测序(RNA-Seq)分析，该分析是由一个肿瘤抑制基因(NtsG)致命的巨型幼虫(LGL)被敲除并结合癌基因Ras的活性形式(RasV12)的过表达引起的，并鉴定了51个在肿瘤盘中显著变化的成熟miRNAs。在致敏遗传背景下的体内肿瘤增强子和抑制子筛选后，我们鉴定了10个肿瘤增强型(TE)miRNAs和11个肿瘤抑制型(TS)miRNAs，它们与ntsG缺陷诱导的肿瘤发生有关。其中，4个TE和3个TS miRNAs具有人类同源基因。从这项研究中，我们还发现了29个miRNAs，尽管它们在ntsG肿瘤中的表达水平发生了变化，但它们在促进或减轻肿瘤发生方面没有明显的作用。这一系统的分析包括RNA-Seq和体内功能研究，有助于根据miRNAs在上皮性肿瘤发生中的表达谱和功能相关性将其分为不同的组，而进化上保守的TE和TS miRNAs为上皮性肿瘤的治疗提供了潜在的治疗靶点。
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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